Produktkatalog2012 Vorderteil CS5.indd

EUROIMMUN Medizinische 

Labordiagnostika 

AG 

Product Catalogue 

Diagnostics for the Determination of Autoantibodies, 

for Infectious Serology and Allergology 

Indirect Immunofl uorescence — ELISA — RIA — Westernblot 

EUROASSAY — EUROLINE — EUROPLUS — EUROArray 

2012



AG 

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Table of Contents 

EUROIMMUN – Company Profile ...............................................................................................................................................3 

Techniques for the Serological Investigation of Antibodies .....................................................................................................5 

Indirect Immunofluorescence: An Easy and Modern Method .......................................................................................................................... 6 

The Indirect Immunofluorescence Test, Performed Using the TITERPLANE Technique ........................................................................... 10 

Recommended Serum Dilutions for Indirect Immunofluorescence ............................................................................................................... 12 

Diagnostically Relevant Systemic Autoantibodies ........................................................................................................................................... 16 

Organ-/Tissue-Specific Autoantibodies ............................................................................................................................................................. 17. 

Antibodies for Infectious Serology .................................................................................................................................................................... 18 

Antibodies for Allergology ................................................................................................................................................................................. 19 

EUROIMMUN Microplate ELISA ........................................................................................................................................................................ 20 

ELISA Automation using the EUROIMMUN Analyzer I ................................................................................................................................... 22 

Incubating the Microplate ELISA ....................................................................................................................................................................... 23 

EUROASSAY: Line Blots in TITERPLANETechnique Format ....................................................................................................................... 24 

Incubating the EUROASSAY (TITERPLANETechnique) ................................................................................................................................ 25 

The EUROLINE: A New Technique for Extensive Antibody Profiles .............................................................................................................. 26 

EUROLINE Automation Using EUROBlotMaster and EUROLineScan ............................................................................................................ 27. 

Westernblots/EUROLINE-WB: Reliable Differentiation of Antibodies Present ............................................................................................... 28 

Incubating the EUROLINE/Westernblot/EUROLINE-WB ................................................................................................................................... 29 

The EUROArray: DNA Microarray Test Systems for Diagnostics (IVD).......................................................................................................... 30 

Performance and Evaluation of the EUROArray Test ...................................................................................................................................... 31 

EUROIMMUN Radioimmunoassays (RIA/IRMA) .............................................................................................................................................. 32 

EUROIMMUN Products for the Determination of Autoantibodies ...........................................................................................33 

Autoantibodies against Cell Nuclei (ANA) ........................................................................................................................................................ 34 

Autoantibodies against Double-Stranded DNA (dsDNA) ................................................................................................................................ 37. 

Autoantibodies against CCP and Sa .................................................................................................................................................................. 38 

Autoantibodies against Mitochondria (AMA) ................................................................................................................................................... 39 

Autoantibodies against Liver Antigens ............................................................................................................................................................. 40 

Autoantibodies against Thyroid Gland Antigens / Antigen Detections .......................................................................................................... 42 

Autoantikörper against Antigens of the Skin ................................................................................................................................................... 43 

Autoantibodies against Neuronal Antigens ...................................................................................................................................................... 44 

Autoantibodies against Islet Cell Antigens ....................................................................................................................................................... 46 

Autoantibodies against Parietal Cells (PCA) ..................................................................................................................................................... 47. 

Autoantibodies against Granulocyte Cytoplasm (cANCA/pANCA) ................................................................................................................. 48 

Autoantibodies against CIBD-relevant Antigens .............................................................................................................................................. 49 

Autoantibodies against Phospholipase A 2 Receptor (PLA2R) ......................................................................................................................... 51 

Antibodies against Endomysium and Gliadin .................................................................................................................................................. 52 

EUROIMMUN Products for Infectious Serology ......................................................................................................................53 

Antibodies against Borrelia ................................................................................................................................................................................ 54 

Antibodies against Epstein-Barr Virus (EBV) .................................................................................................................................................... 56 

Antibodies against Helicobacter Pylori ............................................................................................................................................................. 58 

Antibodies against Herpes Simplex Virus (HSV) ............................................................................................................................................. 59 

Antibodies against Chlamydia ........................................................................................................................................................................... 60 

Antibodies against Emerging Viruses ............................................................................................................................................................... 61 

BIOCHIP Mosaics for Infectious Serology ..................................................................................................................................................... 62 

Additional Reagents for the Determination of Acute Infections ..................................................................................................................... 64 

EUROIMMUN Products for Allergology ...................................................................................................................................65 

Order Information and Product Data .......................................................................................................................................64 

Fluorescence-Labelled Antibodies: Fluorescein (FITC) for EUROIMMUN IIFT ............................................................................................... 69 

Controls for EUROIMMUN IIFT: Organ-Specific Autoantibodies .................................................................................................................... 7.0 

Controls for EUROIMMUN IIFT: Systemic Autoantibodies ............................................................................................................................. 7.2 

Controls for EUROIMMUN IIFT: Infectious Serology ....................................................................................................................................... 7.3 

Controls for EUROIMMUN IIFT: Determination of Further Antibodies .......................................................................................................... 7.9 

EUROASSAY for the Determination of Autoantibodies (Test Systems) ........................................................................................................ 80 

EUROASSAY for Allergology (Test Systems) ................................................................................................................................................... 81 

EUROLINE for the Determination of Autoantibodies (Test Systems) ............................................................................................................. 82 

EUROLINE for Infectious Serology (Test Systems) .......................................................................................................................................... 83 

EUROLINE for Allergology (Test Systems) ....................................................................................................................................................... 83 

Westernblot/EUROLINE-WB for the Determination of Autoantibodies (Test Systems) ................................................................................ 86 

Westernblot/EUROLINE-WB for Infectious Serology (Test Systems) ............................................................................................................. 86 

Microplate ELISA for the Determination of Autoantibodies (Test Systems) ................................................................................................. 88 

EUROArray for Molecular Genetic Determinations (Test Systems) ............................................................................................................... 91 

Radioimmunoassay (RIA) for the Determination of Autoantibodies / Autoantigens / Hormone Determination (Test Systems) .............. 91 

Microplate ELISA for Infectious Serology (Test Systems) .............................................................................................................................. 93 

Microplate ELISA for the Determination of Antibodies against Other Antigens (Test Systems) ................................................................. 98 

Microplate ELISA for the Determination of Hormones and Proteins (Test Systems) ................................................................................... 98 

Allercoat 6 System .......................................................................................................................................................................................... 99 

Diagnostics for Indirect Immunofluorescence: Organ-Specific Autoantibodies ..........................................................................................119 

Diagnostics for Indirect Immunofluorescence: Systemic Autoantibodies ...................................................................................................127. 

Diagnostics for Indirect Immunofluorescence: Infectious Serology .............................................................................................................133 

Diagnostics for Indirect Immunofluorescence: Other Antigens ....................................................................................................................142 

Reagents and Other Items for EUROIMMUN Westernblot and EUROLINE ..................................................................................................143 

Further Reagents for EUROIMMUN IIFT ..........................................................................................................................................................143 

Other Items for EUROIMMUN IIFT ...................................................................................................................................................................144 

General Delivery Conditions .............................................................................................................................................................................145 

Index ......................................................................................................................................................................................146



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Company site groß groenau 

Company branch Rennersdorf 

EUROIMMUN Ag – COMPANY PROFILE 

Company headquarters Luebeck Company branch Dassow 

Company branch Pegnitz 

EUROIMMUN worldwide 

EUROIMMUN was founded in September 1987. and today has its headquarters in Luebeck, Germany. German 

branches are situated in gross groenau near Luebeck (Schleswig Holstein), Dassow (Mecklenburg-Western 

Pomerania), Rennersdorf (Upper Lusatia, Saxony) and in Pegnitz (Upper Franconia, Bavaria). Further 

EUROIMMUN AG subsidiaries can be found in Canada (Mississauga), China (Beijing, Hangzhou), great Britain 

(Wimbledon), Italy (Padua), Poland (Wroc ław), Switzerland (Lucerne), Singapore, South Africa (Cape town), 

Turkey (Istanbul) and the USA (New Jersey). At present EUROIMMUN has 843 employees in Germany, 1031 

worldwide. The company is ISO-certified (EN ISO 9001:2008, EN ISO 13485:2003/CMDCAS). 

EUROIMMUN produces reagents for medical laboratory diagnostics. In the foreground are test systems for 

the determination of various antibodies in patient serum in the diagnosis of autoimmune diseases, infectious 

diseases and allergies. 

The test methods employed are predominantly indirect immunofluorescence, microplate ELISA, various blot 

techniques (Westernblot, EUROASSAY, EUROLINE, EUROLINEWB) and all molecular biology techniques. The 

company is based on worldwide-patented state-of-the-art production methods and microanalysis techniques 

and is one of the world’s leading manu facturers of medical laboratory diagnostics. 

The BIOChIPs are one of EUROIMMUN’s many inventions: paper-thin sheets of glass are coated with cells 

or tissue sections and then cut automatically into millimetre-sized fragments which are subsequently glued 

onto slides using a fully automated device. This BIOChIP technology allows extreme miniaturization and 

standardization of immun bio chemical analyses. With BIOChIP Mosaics made from 30 or more different 

organ sections, cell substrates or defined antigens (EUROPLUS) only mini mum incubation efforts are necessary 

to obtain a detailed antibody profile. 

In EUROIMMUN enzyme immunoassays (ELISA) defined antigens, purified using state-of-the-art biotechnological 

processes, are employed as the antigen substrate. Some of these antigens are synthesized 

in the company’s molecular biology laboratories. EUROIMMUN ELISA are characterized by their excellent 

stability, simple handling and short incubation times, and they are ideal for automated use. All reagents are 

delivered ready-to-use and are exchangeable between different lots. EUROIMMUN offers the largest and most 

differentiated arsenal of enzyme immunoassays worldwide for the diagnosis of autoimmune and infectious 

diseases. 

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The innovative procedures EUROASSAY and EUROLINE developed by EUROIMMUN follow the same test 

principle as the ELISA methods, with the use of the BIOCHIP technology. At EUROIMMUN purified antigens 

are printed in parallel lines at defined positions on membrane strips. Following incubation, users can evaluate 

results visually without additional equipment. These reagents allow in particular the differentiation of 

antibodies that are not clearly defined microscopically by indirect immunofluorescence. EUROASSAY and 

EUROLINE are also em ployed in laboratories where no sophisticated laboratory instruments are available. 

EUROIMMUN produces an extensive range of Westernblot strip test systems and corres ponding reagents 

for confirmation of positive fluorescence and ELISA results as well as clarification of difficult-to-interpret 

results in autoimmune diagnostics, infectious serology and allergology. Refined electrophoretical processes 

have been developed to allow the precise separation of diagnostically relevant proteins from one another. 

Lot-specific evalu ation templates are produced for the evaluation of band patterns. The program ”EURO 

LineScan“ enables fully automated evaluation of membrane-based test systems and simplifies the archiving 

of results with large sample series. 

One of the company’s main strengths is its technical expertise. This encompasses not just the manufacture 

and sale of medical laboratory diagnostics, but also the diagnostic application of the products in a reference 

laboratory which provides highly differential diagnostics. This reference laboratory has set standards 

in Germany, and worldwide is unequalled in the whole field of autoimmune diagnostics. The diagnostic 

spectrum of the laboratory also covers the areas of infectious serology and serological allergy diagnostics. 

The reference laboratory receives hundreds of serum samples daily from all over Germany as well as from 

many other countries. It helps EUROIMMUN customers to secure their results: a large proportion of serum 

samples sent to EUROIMMUN for evaluation are analysed free of charge in order to maintain high standards 

in the laboratories of EUROIMMUN customers. Customers can obtain further technical information from 

experienced scientists in the company, with whom they can also discuss serological problem cases. The 

“Institute for Quality Assurance”, an institution newly founded by EUROIMMUN, organises unbiased quality 

assessments and provides advice in the area of quality management. Moreover EUROIMMUN has established 

the “Institute for experimental Immunology”, which is engaged in basic research. 

In October 2011 the EUROIMMUN workforce included 170 university and college graduates, among these 

biologists, biochemists, chemists, engineers and medical doctors (48 of them holding a doctor’s degree). 

Medical technicians are particularly strongly represented with 111 people, corresponding to EUROIMMUN’s 

activities, as well as biology/chemistry laboratory technicians (81). At present the company is training 51 

young people as biology laboratory assistants, industrial clerks, IT specialists, IT clerks, electronic system 

technicians, electronic technicians for devices and systems, industrial mechanics, lathe operators, cooks, 

business information technology specialists and business economists (dual system). At EUROIMMUN great 

value is placed on advising customers and prospective customers in a factual, technical and commercially 

restrained manner and fully supporting them in the use of our diagnostically demanding products. 

EUROIMMUN products are backed by an energetic and competent sales force, qualified information material, 

didactic test instructions and scientifically based, but nevertheless understandable advertisements in technical 

journals. Advertising material is produced in-house using the latest desktop publishing methods, right up 

until the fully digitalised ready-for-exposure documents. The most important publications and posters are 

translated into many languages. EUROIMMUN has set up an informative homepage on the internet (www. 

euroimmun.com) which is visited extensively internationally. 

Over 3,000 laboratories worldwide use EUROIMMUN diagnostics. 400 of these are in Ger many. The company’s 

development is shaped by continuous growth. Although the diagnostic market in Germany stagnated and 

has become particularly strongly competitive, EURO IMMUN has been able to continue its strong expansion. 

The company is achieving an ever increasing independence from the German market, since more and more 

products are sold abroad. With their quality and standardization, EUROIMMUN products are capturing the 

leading position in the world. 

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INvESTIgATION TEChNIqUES 

— 5 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

— 6 — 

cell with 

antigen 

specific human 

antibody 

FITC 

Indirect Immunofluorescence: An Easy and Modern Method 

FITC 

Pattern homog. AntidsDNA? 

Anti-Histones? 

Pattern nucleolar. Anti- 

PM-Scl? 

FITC-labelled antihuman 

antibody 

Pattern fine-granular. 

Anti-SS-A? Anti-SS-B? 

Pattern cytoplasmic. 

AMA M2? 

Differentiation of antibodies using HEp-2 cells. 

tissue sections 

antigen dots 

BIOCHIP Technology and Mosaics. 

culture cells 

transf. 

cells 

Principle of the Test 

• For the determination of autoantibodies or antibodies against infectious agents, 

cells, tissue sections or purified, biochemically characterized substances are 

used as antigen substrates. 

• If the sample is positive, specific antibodies in the diluted serum sample attach 

to the antigens coupled to a solid phase. 

• In a second step, the attached antibodies are stained with fluorescein-labelled 

anti-human antibodies and visualized with the fluorescence microscope. 

• Positive samples can be titrated in steps. The most suitable titration interval 

is provided by the dilution factor 3.162 (square root of 10). In this way, every 

second step represents in its denominator an integral power of 10 (1 : 10, 1 : 32, 

1 : 100, 1 : 320, 1 : 1000, 1 : 3200, 1 : 10000 etc.). 

Indirect Immunofluorescence: A Standardized Technique for the 

Determination of Autoantibodies and Antibodies against Infectious 

Agents 

• High specificity: positive and negative samples produce a large difference in 

signal strength. Each bound antibody shows a typical fluorescence pattern 

depending on the location of the individual antigens. 

• The entire antigen spectrum of the original subtrate is available, thus allowing 

the detection of a large number of antibodies and achieving a higher detection 

rate. 

• Immunofluorescence enables simultaneous detection of antibodies against 

several biochemically different antigens on one single biological substrate. 

• The indirect immunofluorescence test is the analytical method of choice when 

it would be too difficult or too complicated to prepare the test antigens individually 

for enzyme immunoassays. 

EUROIMMUN’s Innovations for the Standardization and Modernization 

of Indirect Immunofluorescence 

• Activation technique: physically or chemically activated cover glasses are coated 

with cultured cells or tissue sections. Frozen tissue sections are fixed to the 

glass surface by covalent bonding, increasing adhesion more than 100 times 

and thus preventing the substrates from being detached. 

• BIOCHIP Technology: cover glasses coated with biological substrates are cut 

into millimetre-sized fragments (BIOCHIPs) on a machine. This makes it possible 

to obtain ten or more first-class preparations of homogeneous quality per tissue 

section, in the case of cultured cell substrates even several thousands. 

• BIOCHIP Mosaics: using several BIOCHIPs coated with different substrates 

side by side on one and the same reaction field, antibodies against various 

organs or infectious agents can be investigated simultaneously. Detailed antibody 

profiles can thus be established with comparatively little effort, allowing 

the reciprocal determination of the results on different substrates. 

• TITERPLANE Technique: samples or reagents are applied to the reaction fields 

of a reagent tray. The BIOCHIP Slides are then placed into the recesses of the 

reagent tray, where all BIOCHIPs come into contact with the fluids, and the 

individual reactions commence simultaneously. As the fluids are confined in a 

closed space, there is no need for the use of a conventional „humidity chamber“.



AG 


Chemically Activated Cover Glasses for Histochemistry 

• For diagnostics of organ-specific or tissue-specific autoantibodies frozen tissue 

sections of various organs are used. However, formerly, the morphology of 

tissues suffered during incubation in aqueous medium, tissue parts occasionally 

became detached from slides, and the interpretation of results was difficult. 

• Using the activation technique for the first time in histology, we have applied 

solid phase techniques. Firstly, the surface of cover glasses is coated with 

spontaneously reactive aldehyde groups. In a second step, the tissue sections 

are applied to the chemically activated cover glasses (Stöcker, W: European 

Patent No. 0 117 262; U.S. Patent No. 4,647,543). Free amino groups of the tissue 

sections, especially of the hydroxy lysine contained in the collagen, bind to the 

carrier material by covalent bonding. 

• This results in an increased adhesion of frozen tissue sections more than a 

hundredfold and prevents them from being detached during incubation. 

Furthermore, in some cases the activation technique results in a significantly 

better conservation of tissue structures, especially in organs which previously 

exhibited a generally low level of adhesion. Therefore, the tests can be evaluated 

with considerably greater confidence. 

Determination of Low-Avidity Antibodies 

• An alternative principle for the serological diagnosis of fresh infections has been 

established by investigating the antibody avidity. 

• The first reaction of the immune system following an infection is the formation 

of low-avidity antibodies. As the infection proceeds, increasingly antigen-adapted 

IgG is formed, and avidity grows. As long as high-avidity IgG is not yet detected 

in the serum, it can be assumed that the infection is still in an early stage. 

• To identify low-avidity antibodies in a patient’s serum, two immunofluorescence 

tests are performed in parallel: one test is carried out in the conventional way, 

the other one includes urea treatment between incubations with patient’s serum 

and per oxidase-labelled anti-human IgG, resulting in the detachment of lowavidity 

antibodies from the antigens. 

• Low-avidity antibodies are present if the fluorescence intensity is significantly 

reduced (two intensity levels ore more) by urea treatment. 

• The following test kits for avidity determination are available: Toxoplasma 

gondii, Rubella virus, West-Nile virus, CMV, EBV-EA, EBV-CA. 

EUROPLUS System: Combination of conventional immunofluorescence 

substrates and monospecific tests 

• In EUROPLUS immunofluorescence tests antibody detection is performed using 

both tissue sections/cell substrates and monospecifically reacting antigens. 

• Antibodies detected in IFT screening tests can therefore be differentiated or 

confirmed with one and the same reaction field. In some cases, the antigens 

help to extend the antigen spectrum, offering a wider range for screening. 

• BIOCHIPs coated with purified or recombinant antigens are used as monospecific 

substrates. 

• In case of a positive result the antigens fluoresce green in defined areas under 

the microscope. 

• In some EUROPLUS test systems several different antigens are coated on 

one BIOCHIP in separate antigen rows. In this manner, several monospecific 

analyses can be performed using a single BIOCHIP. 

• Available EUROPLUS substrates: MPO, PR3, gliadin GAF-3X, OspC, VlsE, 

Plasmodium falciparum und vivax, gp125, p19. 

Aminoethylaminoproyltrimethoxysilane 

NH 2 

(CH 2)2 

NH 

(CH 2)3 

H3CO Si OCH3 OCH 3 

OH 

glass 

glutardialdehyde 

HC O 

(CH 2)3 

HC O 

frozen tissue section 

HC O 

- 3 CH3OH 

NH2 - H2O N 

- H2O 

(CH2)2 (CH2)2 NH 

(CH 2)3 

Si O 

O 

Si O 

Fixation of frozen tissue sections to glass surfaces 

by covalent bonding. 

(CH 2)3 

(CH 2)3 

low-avide Ab against EBV-CA 

high-avide Ab against EBV-CA 

without urea with urea 

NH 2 

HC 

NH 

O 

frozen tissue section 

N 

HC 

(CH 2)3 

HC 

N 

(CH 2)2 

NH 

(CH 2)3 

Si O 

EUROPLUS: BIOCHIP combination of tissue 

sections / cell substrates (left) and purified 

antigens (right). 

O 

— 7. — 

Investigation 

Techniques



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Investigation 

Techniques 

AP16 IF Plus by DAS. 

— 8 — 


The IF Sprinter: Quick automated processing for reliable IFT results 

• Safe and convenient: Fully automated processing of immunofluorescence tests, 

from the dilution and dispensing of samples to the incubation and washing of 

microscope slides. 

• User-friendly: Sample identification by automatic scanning of barcodes when 

racks are inserted into the system. 

• Quick and reliable results: The washing of slides by flooding ensures short 

processing times and clear immunofluorescence signals. 

• Smooth laboratory routine: The connection to EUROLabOffice (optional) offers 

unique ways to optimise processes in serology, e. g. automatic generation of 

worklists. 

AP16 IF Plus by DAS: Automated Solution for all EUROIMMUN 

Immunofluorescence Tests 

• Various validated parameters. Slide definitions and test files available. 

• CE conformity for device/test system combination. 

• Capacity: 16 slides, 80 samples, 200 dilutions. 

• Programmable for 8 methods per run. 

• 12 dilution series freely programmable. 

• Automated sample dilution, sample and reagent dispension, incubation and 

washing of slides. 

• Laboratory software interface. 

• The incubation protocol for result documentation is automatically created from 

the worklist. 

• Barcode reader available on request. 

• Very simple operation. 

Fluorescence microscope EUROStar III Plus and EUROIMMUN cLED 

• EUROStar III Plus is specifically tailored to the requirements of indirect immunofluorescence. 

The conventional complex illumination fittings have been 

replaced by the stunningly simple EUROStar Bluelight system. 

• The LED has a life expectancy of 50,000 hours – which is 500 times longer than 

a mercury vapour lamp. Its light intensity is maintained at a constant level by 

electronic regulation. Thus, the microscope requires almost no maintenance. 

• Our technicians regularly check the light intensity of your EUROStar III Plus and 

issue a certificate to support your quality management system. 

• LEDs require only a tenth of the electrical power of a 50-watt HBO lamp, at a 

comparable brightness. EUROStar Bluelight provides instant full light output 

every time after being switched on. It does not emit any ultraviolet radiation and 

is explosion-proof. 

• Switching between the camera and the eyepieces is unnecessary due to the 

convenient 50/50 beam splitter. 

• With its halogen transmitted-light source, EUROStar III Plus is suited for brightfield, 

darkfield and, optionally, for phase contrast microscopy. 

• With the EUROIMMUN cLED, the EUROStar Bluelight technology is also available 

as a separate component to upgrade other microscope types.



AG 

BIOCHIP Mosaics 


EUROPattern: Computer-aided immunofluorescence microscopy 

(CAIFM) 

• EUROPattern is a high-performance automation solution designed by EURO- 

IMMUN for the evaluation of immunofluorescence slides in autoimmune 

diagnostics. 

• IIFT patterns and corresponding titers are automatically identified and given for 

each patient individually. 

• Validation and export to LIS are carried out at a mouse click using EUROLabOffice 

(ELO). 

• Automated identification of slides via matrix codes. 

• Evaluation of results at the screen: manual / visual or automated. 

• Automated processing of up to 500 analysis positions in succession. 

• Optionally with automated pattern recognition (HEp-2 / HEp-20-10). 

• Result report per patient (consolidation of single results). 

• Archiving of images and results. 

• No dark room required. 

• Slides for indirect immunofluorescence can be produced with single substrates 

or BIOCHIP Mosaics from up to 60 different substrates according to your 

individual requirements: 

• Tissue sections and cell cultures / smears: adrenal gland, bladder (rat), brain stem, 

cartilage*, cerebellum, cerebrum, colon, Crithidia luciliae sensitive, eye, F-actin 

(VSM47.), granulocytes (fixed with EOH, HCHO or MOH), heart muscle, HEp-2 

cells, HEp-20-10 cells, hippocampus, HUVEC, hypothalamus*, inner ear (rat)*, 

intestinal goblet cells, jejunum, kidney (primate, rat, mouse), lacrimal gland*, 

lactoferrin-specific granulocytes, lip*, lipocytes*, liver (primate, rat, mouse), 

lung*, lymphocytes, mamma*, monocytes*, mouth mucosa*, oesophagus 

(primate, rat), optic nerve (AQP-4, NMO IgG), ovary, pancreas, parathyroid 

gland, parotid gland, peripheral nerve, placenta*, pituitary gland, pons*, 

prostate*, salt-split skin, skeletal muscle, spermatozoa, spinal cord, stomach 

(primate, rat, mouse), substantia nigra*, testis, thrombocytes, thymus*, thyroid 

gland, tongue, umbilical cord, vesicula seminalis* etc. Adenovirus, Bartonella 

henselae, B. quintana, Bordetella parapertussis, B. pertussis, Borrelia afzelii, B. 

burgdorferi (strains CH, USA), B. garinii, Campylobacter coli*, C. jejuni, Candida 

albicans, C. glabrata*, C. krusei*, C. parapsilosis*, C. tropicalis*, Chikungunya 

virus, Chlamydia pneumoniae, C. trachomatis, C. psittaci, CMV, Coxsackievirus 

(A7., A9, A16, A24, B1 to B6), Dengue virus type 1 to 4, EBV-CA, EBNA, EBV-EA, 

Echinococcus granulosus, ECHO virus, hantavirus, Haemophilus influenzae*, 

Helicobacter pylori, HHV-6, HSV-1, HSV-2, Influenza virus A (strains H3N2, H1N1, 

H5N1), Influenza virus B, Japanese encephalitis virus, Klebsiella pneumoniae*, 

Legionella bozemanii*, L. dumoffii*, L. gormanii*, L. jordanis*, L. longbeachae, 

L. micdadei*, L. pneumophila (serotypes 1 to 14), Leishmania donovani, Listeria 

monocytogenes (strains 1/2a, 4b)*, measles virus, mumps virus, Mycoplasma 

hominis, M. pneumoniae, Parainfluenza virus type 1 to 4, Rift valley fever virus, 

RSV, rubella virus, Saccharomyces cerevisiae, sandfly fever virus, SARS-CoV, 

Sindbis virus*, TBE virus, TO.R.C.H. profile, Toxoplasma gondii, Treponema 

pallidum, T. phagedaenis, Ureaplasma urealyticum, usutu virus*, VZV, West Nile 

virus, Yellow fever virus, Yersinia enterocolitica (O:3, O:4, O:6 and O:9)*. 

• EUROPLUS: HEp-2/liver + RNP/Sm, Sm, SS-A, SS-B, Scl-7.0, rib. P-proteins, Jo-1; 

granulocytes + MPO, PR3; primate stomach (parietal cells) + intrinsic factor; 

primate liver (endomysium) + gliadin (GAF-3X); rat kidney + AMA M2; thyroid 

gland + thyroglobulin; renal glomeruli and tubules + GBM; BP180 (NC16A- 

4X); Borrelia burgdorferi and afzelii + OspC and VlsE; EBV-CA + gp125 + p19; 

Plasmodium falciparum (HRP-2, MSP-2); P. vivax (MSP, CSP). 

• Transfected cells: AQP-4, BP230 gc, collagen VII, desmoglein 1 + 3, envoplakin*, 

GABABR, GAD65, glutamate receptors (type NMDA, AMPA*), glycine receptors*, 

IA2*, PLA2R, rPAg 1 + 2 (pancreas antigen 1 + 2), VGKC (CASPR2, LGI1), zinc 

transporter 8*, Crimean Congo fever virus (GPC, N). 

* Currently not available in the European Union. 

— 9 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

— 10 — 

The Indirect Immunofluorescence Test, Performed Using the 

TITERPLANE Technique 

(Reaction fields 5 x 5 mm) 

The TITERPLANE Technique was developed by EUROIMMUN in order to standardize immunological analyses: 

Samples or labelled antibodies are applied to the reaction fields of a reagent tray. The BIOChIP Slides are then 

placed into the recesses of the reagent tray, where all BIOCHIPs of the slide come into contact with the fluids, 

and the individual reactions commence simultaneously. Position and height of the droplets are exactly defined 

by the geometry of the system. As the fluids are confined in a closed space, there is no need for the use of a 

conventional ”humidity chamber”. It is possible to incubate any number of samples next to each other and 

simultaneously under identical conditions. 

Prepare: Check the reagent tray: Are the reaction fields hydrophiIic and the surrounding coating hydro phobic? 

If not, rub with a wet paper towel, using normal household detergent or Extran MA 01 (Merck) if necessary, and 

rinse thoroughly with water. For occasional disinfection, immerse for 1 h in 3% Sekusept Extra (Henkel) in water. 

Open the individual packets containing the BIOCHIP Slides only after they have reached room temperature. Do 

not touch the BIOCHIPs. Mark BIOCHIP Slides as required with a felt pen. 

Dilute: Dilute serum samples according to the user’s test protocol. Include positive and negative controls with 

every test procedure. Mix control sera before use. 

Pipette: Apply 30 µl of diluted serum to each reaction field of the reagent tray, avoiding air bubbles. Transfer all 

samples to be tested before starting the incubation (up to 200 droplets). Use a polystyrene pipetting template. 

Incubate: Start reactions by fitting the BIOCHIP Slides into the corresponding recesses of the reagent tray. 

Ensure that each sample makes contact with its BIOCHIP and that the individual samples do not come into 

contact with each other. Incubate for 30 min at room temperature. 

Wash: Rinse the BIOCHIP Slides with a flush of PBS-Tween using a beaker, and immerse them immediately 

afterwards in a cuvette containing PBS-Tween for at least 5 min. 

Pipette: Apply 20 µl of fluorescein-labelled anti–human immunoglobulin (conjugate) onto each reaction field 

of a clean reagent tray. Add all drops (reagent for a maximum of 50 slides) before continuing incubation. Use 

a stepper pipette. The labelled anti-human serum should be mixed with a pipette before use. To save time, 

conjugate can be pipetted onto separate reagent trays during incubation with the diluted serum. 

Incubate: Remove one BIOCHIP Slide from the PBS-Tween and within five seconds blot only the back and the 

long edges with a paper towel and immediately put the BIOCHIP Slide into the recesses of the reagent tray. Do 

not dry the areas between the reaction fields. Check for correct contact between the BIOCHIPs and liquids. Then 

continue with the next BIOCHIP Slide. From now on, protect the slides from direct sunlight. Incubate for 30 min 

at room temperature. 

Wash: Rinse the BIOCHIP Slides with a flush of PBS-Tween using a beaker and put them in a cuvette containing 

PBS-Tween for at least 5 min. 10 drops of Evans Blue (150 µl) for each 150 ml phosphate buffer can be added for 

counterstaining. 

Embed: Place glycerol/PBS onto a cover glass – drops of 10 µl per reaction field. Use a polystyrene embedding 

template. Remove one BIOCHIP Slide from the PBS-Tween and dry the back and all four edges as well as the surface 

around, but not between, the reaction fields with a paper towel. Put the BIOCHIP Slide, with the BIOCHIPs facing 

downwards, onto the prepared cover glass. Check immediately that the cover glass is properly fitted into the 

recesses of the slide. Correct the position if necessary. Now proceed in the same way with the next BIOCHIP 

Slide. 

Evaluate: Read the fluorescence under the microscope.



AG 

The Indirect Immunofluorescence Test, Performed Using the 

TITERPLANE Technique 

Pipette: 

10 µl per field (3 x 3 mm) 


7.0 µl per field (7. x 9 mm) 

Incubate: 30 min 

Wash: 1 s flush 

5 min cuvette 

Pipette: 



65 µl per field (7. x 9 mm) 



5 min cuvette 

Embed: 



20 µl per field (7. x 9 mm) 

Evaluate: fluorescence microscopy 

slide 

BIOCHIPs 

PBS- 

Tween 

PBS- 

Tween 

20x 

NEOFLUAR 

reagent tray 

diluted samples 

labelled antibody 

glycerol/PBS 

cover glass 

— 11 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

— 12 — 

Recommended Serum Dilutions for Indirect Immunofluorescence 

– Autoimmunity – 

Antibodies against Substrate IgA Igg IgM IgAgM 

acetylcholine receptor *skeletal muscle, monkey / heart, monkey 100 

actin Hepatitis Mosaic**, VSM47. 10 100 + 1000 100 + 1000 

ADH-producing cells nucl. supraopticus & paraventricularis, monkey 10 10 

adrenal cortex adrenal gland, monkey 10 

alveolar basement membrane lung, monkey / kidney, monkey 10 

aquaporin-4 Neurology Mosaic 10 + 100 10 + 100 

asialoglycoprotein receptors *Hepatitis Mosaic** 100 

basic myelin protein (BMP) cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 

bile canaliculi Hepatitis Mosaic** 100 

bile duct epithelium Hepatitis Mosaic** 100 

BP180 Dermatology Mosaic (EUROPLUS) 10 10 + 100 10 + 100 

BP230 Dermatology Mosaic (transfected cells) 10 + 100 10 + 100 10 + 100 

brain: grey matter cerebellum, monkey / intestinal tissue, monkey 10 + 100 10 

brain: white matter cerebellum, monkey / intestinal tissue, monkey 10 + 100 10 

cANCA granulocytes (EOH), human / liver, monkey 10 10 + 100 + 1000 

cartilage trachea, fetal monkey 10 10 

cell nuclei (ANA) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

CENP-F *HEp-2 cells / liver, monkey 10 + 100 + 1000 100 

centromere HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

cerebrum gyrus precentralis, monkey 10 + 100 10 

chondroitin sulfate trachea / cartilage, monkey 10 10 

collagen type VII oesophagus, monkey / transfected cells 10 + 100 10 + 100 

collagenous connective tissue pancreas, monkey 10 10 

colon (epithelial cells) intestinal tissue, fetal monkey 10 10 

cornea eye, monkey 10 

CUZD1 (rPAg1) CIBD Mosaic 10 + 100 10 + 100 

cyclin I (PCNA) HEp-2 cells / liver, monkey 10 + 100 + 1000 100 

cyclin II (mitosin) HEp-2 cells / liver, monkey 10 + 100 + 1000 100 

cytoskeleton HEp-2 cells / liver, monkey 100 10 + 100 + 1000 100 

desmoglein 1+3 Dermatology Mosaic (transfected cells) 10 + 100 10 + 100 10 + 100 

desmosomes oesophagus, monkey or tongue, monkey 10 + 100 10 + 100 10 + 100 

dsDNA Crithidia luciliae 10 10 10 10 

dsDNS-bound laktoferrin CIBD Mosaic 10 10 

elastin stomach, rat / kidney, rat 100 + 1000 

endocardium endocardium, monkey / intestinal tissue, monkey 10 

endomysium liver, monkey 10 10 

endothelial cells skeletal muscle, monkey / HUVEC 100 100 

endplates *skeletal muscle, monkey / heart, monkey 10 + 100 

enterocytes intestinal tissue, fetal monkey 10 10 

eosinophilic granulocytes granulocytes (EOH) / liver, monkey 10 10 + 100 1 

epidermal basement membrane oesophagus, monkey or tongue, monkey 10 + 100 10 + 100 

eye muscle eye, monkey 100 

filaggrin oesophagus, rat 10 10 

GABA-receptor B1 transfected cells 10 + 100 

ganglion cells ganglion stellatum, monkey / intestinal tissue, monkey 10 

gastric mucosa stomach, monkey 10 

gastrin-producing cells stomach (antrum), monkey / stomach (corpus), monkey 10 

glandula suprarenalis adrenal gland, monkey 10 

gliadin *intestinal tissue, fetal monkey / gliadin dots 10 10 

glomerular basement membrane (GBM) kidney, monkey 10 10 

glutamate receptor type AMPA transfected cells 10 + 100 10 + 100 

glutamate receptor type NMDA transfected cells 10 + 100 10 + 100 

glutamic acid decarboxylase (GAD) cerebellum, monkey / pancreas, monkey 10 + 100 10 

goblet cells goblet cells (culture) 10 10 

Golgi apparatus HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

*) In addition to the preferential analysis or as a plausibility check. 

**) Hepatitis Mosaic: liver, monkey / heart, monkey / HEp-2 cells / liver, rat / kidney, rat / stomach, rat.



AG 




GP2 (rPAg2) CIBD Mosaic 10 10 + 100 + 1000 

hair follicle epidermis, monkey 10 10 

heart muscle skeletal muscle, monkey / heart, monkey 100 100 

heart valves mitral valve, monkey 10 10 

histones *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

Hu cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 

hypothalamus nucl. supraopticus & paraventricularis, monkey 10 10 

intercalated discs heart, monkey 100 100 

intestinal epithelial tissue intestinal tissue, monkey 10 10 

intrinsic factor *stomach, monkey / intrinsic factor 10 10 

Jo-1 *HEp-2 cells / liver, monkey 10 + 100 + 1000 100 

keratin oesophagus, monkey or tongue, monkey 10 10 

keratin, RA-associated (filaggrin) oesophagus, rat 10 10 10 10 

Ku *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

labyrinth inner ear, rat or guinea pig 10 10 

lacrimal gland (excretory ducts and acini) lacrimal gland, monkey 10 10 

lamins HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

lipocytes fat tissue, monkey 10 10 

liver membrane (LMA) Hepatitis Mosaic** 100 

liver-kidney microsomes (LKM) Hepatitis Mosaic** 100 

liver-pancreas antigen (LP) Hepatitis Mosaic** / pancreas, monkey 100 

liver-specific protein (LSP) Hepatitis Mosaic** 100 

lymphocytes Lymphocytes 10 + 100 10 + 100 

lysosomes HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

M2 *Hepatitis Mosaic** 100 + 1000 + 10000 100 





M7. *Hepatitis Mosaic** 100 + 1000 + 10000 100 



medullated nerves cerebellum, monkey / nerves, monkey 10 + 100 

melanocytes retina, monkey 10 10 

Mi-2 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

mitochondria (AMA) kidney, rat / stomach, rat / M2 dots / HEp-2 cells 100 + 1000 + 10000 100 

mouth mucosa mouth mucosa 10 

myelin cerebellum, monkey / nerves, monkey 100 100 

myelin-associated glycoprotein (MAG) cerebellum, monkey / nerves, monkey 10 10 10 + 100 10 + 100 

myeloperoxidase (MPO) granulocytes (EOH), human / liver, monkey 10 

myocardium skeletal muscle, monkey / heart, monkey 100 100 

myolemma skeletal muscle, monkey / heart, monkey 10 10 

myosin skeletal muscle, monkey / heart, monkey 100 

native collagen pancreas, monkey 10 

nerves cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 

neuroendothelium cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 

neurofilaments cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 

NOR HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

nRNP HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

ovary ovary, monkey 10 10 

pANCA granulocytes (EOH), human / liver, monkey 10 10 + 100 + 1000 

pancreas acini (Crohn’s disease autoantigen) pancreas, monkey 10 + 100 10 + 100 

pancreas islets pancreas, monkey (1st step: 18 hours) 10 + 100 

pancreas, excretory duct epithelium pancreas, monkey 10 + 100 10 + 100 

parathyroid gland parathyroid gland, monkey 10 

*) In addition to the preferential analysis or as a plausibility check. 

**) Hepatitis Mosaic: liver, monkey / heart, monkey / HEp-2 cells / liver, rat / kidney, rat / stomach, rat. 

— 13 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

parietal cells stomach (corpus), monkey 10 10 10 + 100 

parotid gland parotid gland, monkey 10 10 

peripheral nerves cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 

pituitary gland, anterior lobe pituitary gland, monkey 10 10 

placenta placenta, human 10 

PM-1 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

prostate prostate, monkey 10 

proteinase 3 (PR3) granulocytes (EOH), human / liver, monkey 10 10 + 100 + 1000 

Purkinje cell cytoplasm (Yo) cerebellum, monkey 10 + 100 10 + 100 

RANA Raji cells / HEp-2 cells 10 10 

reticulin intestinal tissue, fetal monkey 10 10 10 

retina retina, monkey 10 10 

Ri cerebellum, monkey / nerves, monkey / intestinal tissue, fetal monkey 10 + 100 10 + 100 

ribosomes HEp-2 cells / liver, monkey 10 + 100 + 1000 100 

RNA polymerase HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

RNA HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

salivary glands (acini and excretory ducts) parotid gland, monkey 10 10 

sarcolemma skeletal muscle, monkey / heart, monkey 100 10 

Scl-7.0 HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

signal recognition particle (SRP) HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

skeletal muscle skeletal muscle, monkey / heart, monkey 100 100 

Sm HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

smooth muscles (ASMA) stomach, rat / kidney, rat 100 + 1000 100 + 1000 

spermatozoa spermatozoa smear, human 10 10 10 

spindle fibers HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

spleen spleen, monkey 10 + 100 

SS-A (Ro) *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

SS-B (La) *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

ssDNA *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

striated muscles skeletal muscle, monkey / heart, monkey 100 + 1000 100 + 1000 

substantia nigra substantia nigra, monkey 10 + 100 

testis testis, monkey 10 

thrombocytes (bound antibodies) thrombocyte smear – – – 

thrombocytes (free antibodies) thrombocytes, human 10 10 10 

thymus thymus, monkey 10 10 10 

thyroglobulin thyroid gland, monkey or struma, human/TG 10 + 100 10 

thyroid colloid type II thyroid gland, monkey or struma, human 10 10 

thyroid microsomes thyroid gland, monkey or struma, human 10 10 

trachea trachea, monkey 10 10 

tubular basement membrane kidney, monkey 10 10 

VGKC (CASPR2 + LGI1) transfected cells 10 + 100 10 + 100 

U1-nRNP *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

vasopressin-producing cells nucl. supraopticus & paraventricularis, monkey 10 10 

vestibular organ inner ear, rat or guinea pig 10 10 

vimentin *HEp-2 cells / liver, monkey 100 + 1000 + 10000 100 

”xANCA” granulocytes (EOH, HCHO) / liver, monkey 10 10 + 100 1 

— 14 — 




*) In addition to the preferential analysis or as a plausibility check.



AG 


– Infectious Serology – 

Antibodies against IgA Igg IgM 

Adenovirus (type 3) 10 + 100 10 + 100 10 

Bartonella henselae 320 + 1000 100 

Bartonella quintana 320 + 1000 100 

Bordetella parapertussis 10 + 100 100 + 1000 100 + 1000 

Bordetella pertussis 10 + 100 100 + 1000 100 + 1000 

Borrelia afzelii 100 + 320 + 1000 10 

Borrelia burgdorferi (strains CH and USA) 100 + 320 + 1000 10 

Borrelia garinii 100 + 320 + 1000 10 

Borrelia OspC 10 

Borrelia VlsE 100 

Campylobacter coli 100 100 + 1000 10 

Campylobacter jejuni 320 1000 100 

Candida albicans 1000 3200 + 10000 320 

Candida glabrata 1000 1000 + 3200 + 10000 320 

Candida krusei 1000 1000 + 3200 + 10000 320 

Candida parapsilosis 1000 1000 + 3200 + 10000 320 

Candida tropicalis 1000 1000 + 3200 + 10000 320 

Chikungunya virus 10 + 100 10 + 100 

Chlamydia pneumoniae (IFA) 100 100 + 1000 10 

Chlamydia pneumoniae (MIF) 10 100 10 

Chlamydia trachomatis (IFA) 100 320 + 1000 10 

Chlamydia trachomatis (MIF) 10 100 10 

Chlamydia psittaci (MIF) 10 100 10 

CMV 100 100 + 1000 100 

Coxsackie virus types A7., A9, A16, A24, B1 to B6 10 + 100 100 + 1000 10 

Crimean Congo fever virus 100 + 1000 10 + 100 

Dengue virus 100 + 1000 10 + 100 

EBV-CA, -EA 10 + 100 10 + 100 + 1000 10 + 100 

EBNA 10 + 100 

Echinococcus granulosus 100 100 + 320 + 1000 100 

Echo virus (type 7., 19) 10 + 100 100 + 1000 10 

Hanta virus 100 + 1000 100 + 1000 

Haemophilus influenzae 100 1000 + 10000 10 

Helicobacter pylori 32 + 100 100 + 1000 10 

HHV-6 10 + 100 10 

HSV-1/2 10 100 + 1000 + 10000 10 

Influenza virus type A 10 10 + 100 10 

Influenza virus type B 10 10 + 100 10 

Japanese encephalitis virus 10 + 100 + 1000 10 + 100 

Klebsiella pneumoniae 100 100 100 

Legionella pneumophila (all serotypes) 100 + 320 + 1000 

Leishmania 100 320 100 

Listeria monocytogenes (type 1/2a, 4b) 100 100 + 1000 100 

measles virus 10 + 100 10 

mumps virus 10 + 100 10 

Mycoplasma pneumoniae 10 10 + 100 10 

Parainfluenza virus types 1 - 4 10 + 100 10 + 100 + 1000 10 

Plasmodium falciparum/vivax 32 + 100 

Rift valley fever virus 100 + 1000 10 + 100 

rubella virus 10 + 100 

RSV 10 10 + 100 + 1000 10 

Saccharomyces cerevisiae 100 1000 100 

Sandfly fever virus 100 + 1000 100 + 1000 

SARS coronavirus 10 10 + 100 10 

TBE virus 10 10 + 100 + 1000 10 + 100 

Toxoplasma gondii 16+64+256 16+64+256+1028... 16+64+256 

Treponema pallidum 10 10 + 100 10 

VZV 10 10 + 100 10 

West-Nile virus 10 + 100 + 1000 10 + 100 

Yellow fever virus 100 + 1000 10 + 100 

Yersinia enterocolitica O:3; O:4; O:6; O:9 10 + 100 100 10 + 100 

— 15 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

Prof. Dr. Winfried Stöcker 

Clinical Pathologist 

Ig- AGM A G M BASIS SPECTRUM 

151 ANA (cell nuclei) IF global testing 

152 ANA profile differentiation 

1572 dsDNA-NcX ELISA 

1572 dsDNA IFT SLE specific 

1590 ENA ProfilePlus ELISA 1 

nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1 

1590 ENA ProfilePlus ELISA 2 

rib. P proteins, RNP/Sm, Sm, SS-A, 

SS-B, Scl-70, Jo-1, CENP B 

1590 SLE Profile ELISA (dsDNA, histones, rib. 

P prot., nRNP/Sm, Sm, SS-A, SS-B, Scl-70) 

162 AMA (mitochondria) 

171 ASMA (smooth muscle) 

120 cANCA* (granulocytes) Wegener’s dis. 

121 pANCA* (granulocytes) vasculitis 

1030 autoantibody profile 30 IF substrates 

Ig- AGM A G M ANA DIAGNOSTICS, WESTERNBLOT 

1520 PM-Scl, CENP A/B, Ku 86 and 72 kDa, 

M2 74 kDa, RNP 70 kDa, RNP A/C, 

Sm B/B’/D, SS-A 60 and 52 kDa, Ro-52, 

SS-B 52, 47, 44 and 43 kDa, ribosomal 

P proteins P0/P1/P2, Scl-70, Jo-1) 

Ig- AGM A G M OTHER AUTOANTIBODIES 

1612 centrioles 

1613 MSA-1 (NuMa, spindle fibres) 

1614 MSA-2 (midbody) 

1615 MSA-3 (chromosome-ass. antigen) 

1617 centromer F protein (CENP-F) 

1641 ribosomes 

1642 Golgi apparatus 

1643 lysosomes 

165 cytoskeleton 

1651 actin 

1652 vimentin 

1653 cytokeratin 

1654 tropomyosin 

1655 vinculin 

1656 desmin 

1659 laminin (basal membranes) 

1947 collagen type VII 

1950 elastin 

196 vessel endothelium 

Ig- AGM A G M THERAPY CONTROL 

1821 interferon alpha*** 

1822 interferon beta 

1824 erythropoetin 

1572 dsDNA RIA 

1818 CIC-C1q ELISA 

— 16 — 

Clinical Immunology Laboratory 

Seekamp 31 

D-23560 Lübeck (Germany) 

Telephone +49 451 58 55 986 

Fax 58 55 134 

Diagnostically Relevant Autoantibodies 

Systemic Autoantibodies against 

Ig- AGM A G M SYST. LUPUS ERYTHEMATOSUS (SLE) 


1574 nucleosomes SLE specific 

1571 dsDNA ELISA SLE specific 

1572 dsDNA-NcX ELISA SLE specific 

1572 dsDNA IFT (C. luciliae) SLE specific 

1572 dsDNA RIA SLE specific 

159 ENA PoolPlus ELISA 

1591 U1-nRNP (70K, A, C) 

1593 Sm SLE specific 

1595 SS-A (Ro) 60 kDa: native 

159s Ro-52: recombinant 

1597 SS-B (La) 

1640 ribosomal P proteins SLE specific 

1605 Ku 

1601 cyclin I (PCNA) 

156 histones (global testing) 

1576 ssDNA (single-stranded DNA) 

121 pANCA* (granulocytes) vasculitis 

Ig- AGM A G M SJÖGREN’S SYNDROME 


1595 SS-A (Ro) 60 kDa: native 


1597 SS-B (La) 

Ig- AGM A G M ANTI-PHOSPHOLIPID 

SYNDROME (APS) 

1621 cardiolipin 

1632 ß-2-glycoprotein 1 

1631 lupus anticoagulant (plasma)** 

162a phosphatidylserine 

Ig- AGM A G M SYSTEMIC SCLEROSIS 

(DIFFUSE + LIMITIERTE FORM) 


1532 Systemic Sclerosis Profile EUROLINE 

(Scl-70, CENP A, CENP B, RP11, RP155, 

Fibrillarin, NOR90, Th/To, PM-Scl100, 

PM-Scl75, Ku, PDGFR, Ro-52) 

1599 Scl-70 (DNA topoisomerase I) 

1584 PM-Scl75 (75 kDa) 

1584 PM-Scl100 (100 kDa) 

1611 centromeres 

1611 centromere A and B protein (rec.) 

1582 U3-nRNP (fibrillarin) 

1583 RNA polymerase I, II, III 

1585 7-2-RNP (Th/To) 

1586 4-6-S-RNA 

1587 NOR (nucleolus organizer region) 

1605 Ku 

CIRC. IMMUNE COMPLEXES 

1818 C1q ELISA 

Ig- AGM A G M SHARP’S SYNDROME MCTD 

1591 U1-nRNP (70K, A, C) 


Ig- AGM A G M POLYMYOSITIS, DERMATOMYOSITIS 


1530 Myositis Profile 3 EUROLINE 

(Mi-2, Ku, PM-Scl100, PM-Scl75, SRP, Jo-1, 

PL-7, PL-12, OJ, EJ, Ro-52) 

1661 Jo-1 

1662 PL-7 

1663 PL-12 

1664 OJ 

1665 EJ 

1584 PM-Scl75, PM-Scl100 

1616 SRP (signal recognition particle) 


1605 Ku 

1607 Mi-2 

1635 serotonin ab 

1636 PMR (polymyalgia rheumatica factor) 

Ig- AGM A G M (RHEUMATOID) ARTHRITIS 

1505 CCP (cyclic citrullinated peptides) 

151a Sa 

1814 RF (class. rheumatoid factor) 

1508 filaggrin (RA keratin) 

1219 GS ANA (granulocyte specific ANA) 


1604 RANA (rheum. arthritis nuclear antigen) 

121 pANCA* (granuloc.) RF-ass. vasculitis 

148 cartilaginous subst. polychondritis 

1947 collagen type VII 

FURTHER RHEUMATOID RELEVANT 

Ig- AGM A G M ANALYSES 

2011 anti-streptolysin 

2012 anti-streptokinase 

2013 anti-streptodornase 

2014 anti-DPNase (anti-NADase) 

2031 anti-staphylolysin 

2034 anti-hyaluronidase 

213 Borrelia burgdorferi 

2171 Yersinia enterocolitica O:3 

2191 Chlamydia trachomatis 

IMMUNOGLOBULINS: 

Ig- AGM A G M ANTI- 

1811 human IgA 

1813 human IgE 

1814 human IgG 

1815 human IgM 

Grey boxes: standard analysis *) ANCA diagnostics in acute cases within one hour, at any hour **) Use special procedure for taking sample(s) ***) Send frozen sample(s) 

Fax:



AG 



Ig- AGM A G M AUTOANTIBODY PROFILE 

1030 30 IF substrates (BIOCHIPs) 

Ig- AGM A G M THYROID GLAND 

1015 TRAb (TSH receptors) 

1012 TPO ab (thyroidea peroxidase) 

1013 TAb (thyroglobulin) 

1014 colloid antigen II ab 

1011 MAb (microsomes) 

1016 T 3 ab 

1017 T 4 ab 

Ig- AGM A G M DIABETES MELLITUS 

1021 ICA (islet cell antibodies) 

1022 GAD (glutamic acid decarboxylase) 

1023 IA-2 (tyrosine phosphatase) 

1024 insulin ab human 

1025 insulin receptor 

1026 glucagon-producing cells 

1027 zink transporter 8 

147 lipocytes 

Ig- AGM A G M (POLY-)ENDOCRINOPATHY 

1051 adrenal cortex Addison’s dis. 

1053 21-hydroxylase Addison’s dis. 

1061 ovary: theca cells 

1062 ovary: corpus luteum 

1081 testis: Leydig cells 

105 steroid hormon-producing cells 

104 parathyroid gland 

1021 ICA (islet cell antibodies) 

1012 TPO ab (thyroidea peroxidase) 

1361 H + /K + -ATPase ab ELISA 

1361 PCA (parietal cells) 

1091 pituitary gland: anterior lobe 

1092 pituitary gland: posterior lobe 

1011 MAb (thyroid microsomes) 

1052 adrenal medulla 

107 placenta 

110 VPZ (vasopr.-prod. cells) D. insipudus 

Ig- AGM A G M INFERTILITY 

1621 cardiolipin 

1060 ovary: theca c., c. luteum, z. pellucida 

1081 testis: Leydig cells 

1086 spermatozoa 

1091 pituitary gland: anterior lobe 

107 placenta 

1401 prostate 

Ig- AGM A G M EPIDERMIS 

1501 desmosomes pemphigus 

1495 desmoglein 1 pemphigus 

1496 desmoglein 3 pemphigus 

1491 envoplakin paraneopl. pemphigus 

1502 epiderm. basal membr. pemphigoid 

1502 BP180 bullous pemphigoid 

1502 BP230 bullous pemphigoid 

135 oral mucosa Behçet’s/ Crohn’s dis. 

1503 basal membrane (urinary bladder) 

1509 epidermal keratin 

191 endomysium GSE, Duhring’s dis. 

3011 gliadin GSE, Duhring’s dis. 

1502 herpes gestationis factor 

1504 melanocytes 

150h hair follicle 

1947 collagen type VII NC1 

Ig- AGM A G M EYE 

1178 recoverin 

1177 tunica choroidea chron. chorioretinitis 

1171 cornea 

1172 retina 

1173 lens oculi 

1174 corpus ciliare 

1175 eye muscles 

1176 retro bulbar connective tissue 

120 cANCA* (granulocytes) Wegener’s dis. 


Ig- AGM A G M IMMUNOHAEMATOLOGY 

124 erythrocytes (global testing) 

1209 granulocyte membrane 

1221 lymphocytes 

1231 thrombocytes: indirect test (free ab) 

1232 thrombocytes: direct test (bound ab)** 

1361 H + /K + -ATPase ab ELISA 

1361 PCA (parietal cells) 


Seekamp 31 


Telephone +49 451 58 55 986 

Fax 58 55 134 

Diagnostically Relevant Autoantibodies 

Organ-/Tissue-Specifi c Autoimmunity: Autoantibodies against 

Ig- AGM A G M ANCA-ASSOC. VASCULITIDES 

(WEGENER’S DIS., MICR. ARTERITIS, 

CHURG-STRAUSS SYNDROME)* 

120 cANCA IFT* granuloc. Wegener’s dis. 

1201 PR3 (proteinase 3) 

1202 BPI (CAP 57) 

121 pANCA IFT* granulocytes vasculitis 

1211 MPO (myeloperoxidase) 

1212 elastase 

1213 cathepsin G 

1215 lactoferrin 

120 ANCA Profile ELISA 

PR3, MPO, elastase, cath. G, BPI, lactoferrin 


195 elastin 

196 vessel endothelium 

Ig- AGM A G M KIDNEY, LUNG 

120 cANCA IFT* granuloc. Wegener’s dis. 

121 pANCA IFT* granulocytes vasculitis 

125 kidney IF global testing 

1251 GBM ELISA glomerular basal membrane 

1254 PLA2R idiop. membr. nephropathy 


1572 dsDNA IFT 

1252 TBM (tubular basal membrane) 

1271 lung alveolar basal membrane 

Ig- AGM A G M NERVOUS SYSTEM 

111 Neuronal Ab IFT global testing 

Paraneoplastic neurol. syndromes 

1111 Neuronal Antigens Profile 2 

EUROLINE amphiphysin, CV2.1***, 

PNMA2 (Ma-2), Ri, Yo, Hu 

1112 Tr (Purkinje cell cytoplasm) 

1113 Yo (Purkinje cell cytoplasm; PCA-1) 

1114 PCA-2 (Purkinje cell cytoplasm) 

1115 Ri (neurone nuclei; ANNA-2) 

1116 Hu (neurone nuclei; ANNA-1) 

112d NMDA receptors 

112k AMPA receptors (GluR1, GluR2) 

112l GABA B receptors 

1117 Ma1/Ma2 (neurone nuclei; Ta) 

1119 CV2 (CRMP-5) 

1022 GAD stiff-person syndr. 

112e amphiphysin stiff-person syndr. 

112a AGNA (anti-glia nuclear antigen; SOX-1) 

112b ANNA-3 

1439 potassium channels (VGKC) 

1439 LGI1 

1439 CASPR2 

further parameters 

1154 aquaporin-4 neuromyelitis optica 

1157 glycine receptors 

1156 MOG (myelin-oligodendroc. glykoprot.) 

1121 myelin 

1122 MBP (myelin-basic protein) 

1123 MAG (myelin-assoc. glycoprotein) 

1124 myelin of peripheral nerves 

1126 neuroendothelium 

1127 neurofilaments 

1128 GFAP (glial fibrillary acidic protein) 

1129 non-medullated nerves 

112f astrocytes 

112g basal ganglia 

112h ganglion stellatum 

112i plexus myentericus 

1130 ganglioside profile 

GM 1 , GM 2 , GM 3 , GD 1a , GD 1b , GT 1b , GQ 1b 

113 single ganglioside analysis: 

GM 1 GM 2 GM 3 GD 1a 

GD 1b GT 1b GQ 1b 


213 Borrelia burgd.: serum CSF 

Ig- AGM A G M SKELETAL MUSCLE, THYMUS 

1435 acetylcholine receptors M. gravis 

1434 MuSK M. gravis 

1437 calcium channels (VGCC) LEMS 

1439 potassium ch. (VGKC) neuromyotonia 

1439 CASPR2 neuromyotonia 

144 thymus M. gravis, thymoma 

1431 titin M. gravis 

143 skeletal muscle M. gravis 

1432 sarcolemma 

1436 myosin 

Ig- AGM A G M LIVER, BILIARY DUCTS 

130 Liver Ab IFT global testing, 6 BIOCHIPs 

130 Autoimmune Liver Dis. Ab Profile 

EUROLINE AMA-M2, 3E (BPO), Sp100, 

PML, gp210, LC-1, LKM-1, SLA/LP, Ro-52 

Autoimmune hepatitis (AIH) 

1302 SLA/LP (soluble liver antigen) 

1651 F-actin 


1307 LC-1 (liver cytosol) 

132 LKM (liver kidney microsomes) 

1321 LKM-1 ELISA 

1322 LKM-2 

1323 LKM-3 

1303 ASGPR (asialoglycoprotein receptors) 

171 ASMA (smooth muscles) 

1301 LSP (liver-specific protein) 

1304 LMA (liver cell membrane) 

Primary biliary cirrhosis (PBC) 

162 AMA (mitochondria) 

1622 AMA-M2 (PDH + BPO) 

1624 AMA-M4 (sulfitoxidase) 

1629 AMA-M9 (glycogen phosphorylase) 

1603 Sp100, PML (nuclear dots) 

1608 gp210 (nuclear membrane, lamin) 

Primary-sclerosing cholangitis (PSC) 

121 pANCA (granulocytes) 

further antibodies 

1305 bile ducts 

1306 bile canaliculi 

1609 coilin; P80 (few nuclear dots) 

Ig- AGM A G M STOMACH, INTESTINE 

1361 PCA (parietal cells) atroph. gastritis 

1361 H + /K + -ATPase ab atroph. gastritis 

1362 intrinsic factor ab vit. B 12 deficiency 

1366 gastrin (G) cells 

1391 pancreas acinus cells Crohn’s dis. 

1391 CUZD1 Crohn’s dis. 

1392 GP2 Crohn’s dis. 

2841 Saccharomyces cerev. Crohn’s dis. 

1392 pankreas secretion Crohn’s dis. 

135 mouth mucosa Behçet’s/ Crohn’s dis. 

1381 intestinal goblet cells ulc. colitis 

121 pANCA (granulocytes) ulc. colitis 

1382 enterocytes Crohn’s dis. , ulc. colitis 

191 endomysium GSE, Duhring’s dis. 

191 transglutaminase GSE, Duhring’s dis. 

3011 deamidated gliadin (Z-AGFA) GSE 

192 reticulin GSE, Duhring’s dis. 

EXOCRINE GLANDS, PANCREATITIS, 

Ig- AGM A G M SJÖGREN’S SYNDROME 

139 exocrine pancreas 

1391 pancreas acini 

1393 pancreas excretory ducts 

142 salivary glands (parotid gland) 

1421 parotid gland acini 

1423 parotid gland excretory ducts 

141 lacrimal gland 

Sjögren’s syndrome 


1595 SS-A (Ro) 

1597 SS-B (La) 

1576 ssDNA (single-stranded DNA) 

further antibodies 

1401 prostate 

1406 mamma 

Ig- AGM A G M HEART 

1627 AMA-M7 (myocard-specific) 

146 heart muscle 

1462 heart: intercalated disk 

1463 heart: myolemma 

Ig- AGM A G M LIPODYSTROPHY 

147 lipocytes 

Ig- AGM A G M ANTIBODIES AGAINST ANIMAL IgG 

3811 HAMA (human anti-mouse IgG) — 17. — 

Grey: standard *) ANCA diagn. in acute cases within 1 h **) Special procedure for taking sample ***) CV2 partial protein, which only contains the N-terminally localised epitopes of the antigen 

Investigation 

Techniques



AG 

Investigation 

Techniques 



— 18 — 

IFT 

ELISA 

Westernblot 

EUROLINE 

Ig- AGM A G M BACTERIA A-Z 

219b Bartonella henselae 

219d Bartonella quintana 

2055 Bordetella parapertussis 

2050 Bordetella pertussis 

2131 Borrelia afzelii 

2132 Borrelia burgd. s. stricto 

CSF diagnostics 

2133 Borrelia burgd. (USA) 

2134 Borrelia garinii 

2092 Campylobacter coli 

2091 Campylobacter jejuni 

2192 Chlamydia pneumoniae 

2193 Chlamydia psittaci 

2191 Chlamydia trachomatis 

2040 Diphtheria toxoid 

2070 Haemophilus infl uenzae 

2080 Helicobacter pylori 

2101 Klebsiella pneumoniae 

2150 Legionella pneumophila 

serotypes .................. 

216 Legionella 

dumoffi i gormanii 

jordanis longbeachae 

micdadei 

2140 Listeria monocytogenes 

1/2a 4b 

2201 Mycoplasma hominis 

2202 Mycoplasma 

pneumoniae 

2060 Tetanus toxoid 

2111 Treponema pallidum 


2205 Ureaplasma urealyticum 

2170 Yersinia enterocolitica 

O:3 O:4 O:6 O:9 

Ig- AGM A G M PARASITES A-Z 

2320 Echinococcus gran. 

2231 Leishmania donovani 

2261 Plasmodium vivax 

2264 Plasmodium falciparum 

2410 Toxoplasma gondii 

Avidity determination 

Grey: standard analyses *) Currently not available as IVD in the European Union 

SI_0000_I_UK_A07, 07/2011 

Antibodies for Infectious Serology 

Respiratory tract 

Exanthema 

Lymphadenitis 

CNS 

Myocarditis 

Infectious arthritis 

Gastrointestinal tract 

Associated hepatitis 

Ophthalmology 

Antibodies against 

Otitis 

STD 

Pregnancy 

IFT 

ELISA 

Westernblot 

EUROLINE 

Fax: 


Seekamp 31 


Telephone +49 451 58 55 986 

Fax 58 55 134 

Ig- AGM A G M VIRUSES A-Z 

2680 Adenovirus type 3 

2730 Coxsackievirus type 

B1 B2 B3 B4 B5 

B6 A7 A9 A16 A24 

2570 Cytomegalovirus 


275a Echovirus type 7 

2791 Epstein-Barr virus 

capsid Ag (EBV-CA) 



early Ag (EBV-EA) 


nuclear Ag (EBNA) 

2531 HSV-1 

2532 HSV-2 

2511 HIV-1* 

2512 HIV-2* 

2536 Human herpes virus 6 

(HHV-6) 

2691 Infl uenza virus type A 

H1N1 H3N2 

2692 Infl uenza virus type B 

2610 Measles virus 


2630 Mumps virus 


2720 Parainfl uenza virus type 

1 2 3 4 

2670 Respiratory syncytial 

virus (RSV) 

2590 Rubella virus 



2661 TBE virus 

2650 Varicella zoster virus 


Ig- AGM A G M FUNGI A-Z 

2861 Candida albicans 

2862 Candida glabrata 

2863 Candida krusei 

2865 Candida parapsilosis 

2864 Candida tropicalis 

2841 Saccharom. cerevisiae 

Respiratory tract 

Exanthema 

Lymphadenitis 

CNS 

Myocarditis 

Infectious arthritis 

Gastrointestinal tract 

Associated hepatitis 

Ophthalmology 

Otitis 

STD 

Pregnancy


Date of sample: Type of sample: 


AG 

Diagnosis: 

.................................................................................................................................................................................................. 

GLOBAL TEST 

3840 Determination of total IgE (ELISA) 

INHALATION 

3110 Allergy Profi le Inhalation 

(g1, g3, g6, g12, t2, t3, t4, t7, w1, w6, w9, 

d1, d2, e1, e2, e3, m1, m2, m3, m6, CCD) 

3110 Allergy Profi le Inhalation 2 

(g6, g12, t2, t3, t4, w6, w9, d1, d2, e1, e2, e3, e6, 

e82, e84, es4, m1, m2, m3, m6, CCD) 

3111 Allergy Profi le Pediatric Inhalation 

(g6, g12, t2, t3, t4, w6, w8, w9, d1, d2, e1, 

e2, e3, e6, e82, e84, m1, m2, m3, m6, CCD) 

3112 Allergy Profi le Mediterranean Inhalation 

(g2, g6, t3, t4, t9, t11, t23, t210, w1, w6, w9, w19, 

d1, d2, d70, e1, e2, e3, m2, m6, CCD) 

3113 Allergy Profi le Inhalation „South East Asia“ 

(ts19, t104, t19, t223, gs1, ds1, i6, u134, e1, 

e2, es172, e6, e71, e82, e84, ms1, ms4, m5, 

m12, m45, CCD) 

3116 Allergy Profi le Inhalation “China“ 

(gs23, ts21, t3, t8, t11, t12, t14, t70, ws18, w1, w6, 

w9, es1, d1, d2, i6, ms5, m1, u73, u80, CCD) 

3116 Allergy Profi le Inhalation “China 2“ 

(ds1, h1, i6, e1, e2, ms1, ts20, u80, 

w1, w6, CCD) 

3117 Allergy Profi le Inhalation “Middle East“ 

(g1, g6, g12, t2, t3, t7, t9, w1, w6, w8, d1, d2, 

i6, e1, e84, m1, m2, m3, m5, m6, CCD) 

3118 Allergy Profi le Inhalation “Gulf“ 

(g6, g12, t2, t3, t7, t9, w1, w6, d1, d2, i6, e1, 

e2, e3, e17, m1, m2, m3, m5, m6, CCD) 

3119 Allergy Profi le Inhalation “Turkey 1” 

(gs12, gs15, gs21, g12, ts23, ts24, t9, t70, ws18, 

ws19, ws20, d1, d2, i6, es2, es172, e1, e2, e3, e4, 

e80, e81, e84, ms11, ms12, m1, m2, m3, m6, CCD) 

3119 Allergy Profi le Inhalation “Top Screen” 

(ds1, e1, e2, e81, gs12, g12, t3, t9, 

w1, w6, w19, m2, IgE, CCD) 

3120 Allergy Profi le Inhalation “India“ 

(g6, g12, g20, t18, w4, w27, w29, ds1, d2, i6, e1, e2, 

e11, e85, m3, m37, u81, u126, u129, u140, CCD) 

3121 Allergy Profi le Inhalation “Screen France“ 

(hs12, es1, gs4, ts4, ws2, ms1, CCD) 

Serum ................................................................. 

Antibodies for Allergology 

Sample number: 

Allergen Profi les: Antibodies of class IgE against 

FOOD 

3410 Allergy Profi le Food 

(f1, f75, f2, f45, f4, f5, f9, f13, f14, 

f17, f20, f49, f84, f237, f25, f31, 

f35, f85, f3, f23, CCD) 

3410 Allergy Profi le Food 2 

(f1, f75, f2, f78, f4, f5, f14, f10, f13, 

f17, f20, f49, f84, f95, f25, f31, f35, 

f85, f3, f23, CCD) 

3411 Allergy Profi le Food “South East Asia 1“ 

(f1, f75, f2, f4, f9, f10, f14, f13, f17, 

f63, f64, f83, fs10, fs14, f23, f24, 

f80, f234, f105, f336, CCD) 

3411 Allergy Profi le Food “South East Asia 2“ 

(f1, f75, f2, f4, f9, f10, f14, f13, f17, f63, 

f340, f83, fs10, fs14, f23, f24, f80, f234, 

f105, f336, CCD) 

3414 Allergy Profi le Food “China“ 

(f1, f2, f4, f7, f27, f88, fs35, f13, f14, 

fs40, f25, f292, fs42, f23, f234, f3, 

f41, f56, fs41, fs77, CCD) 

3414 Allergy Profi le Food “China 2“ 

(f1, f2, f13, f14, f23, f24, fs33, fs34, CCD) 

3415 Allergy Profi le Food “Middle East“ 

(f1, f75, f2, f78, e204, f4, f14, f45, f13, 

f17, f20, f33, f49, f92, f25, f31, f85, 

f48, f88, f89, CCD) 

3416 Allergy Profi le Food “Gulf“ 

(f1, f75, f2, f105, f4, f14, f45, fs36, f13, 

f92, f33, f44, f93, f25, f31, f48, f83, 

f88, f3, f23, CCD) 

3420 Allergy Profi le Food “Turkey 1” 

(f1, f75, f2, f169, f78, f4, f79, f9, f14, f10, f13, f17, 

f144, u87, f222, f73, f33, f44, f49, f92, f84, f146, 

f328, f25, f31, f35, f48, f95, f97, f122, f132, fs14, 

fs10, fs43, f83, CCD) 

3421 Allergy Profi le Food “India“ 

(f2, f75, f168, f4, f9, f14, f13, f36, f49, f50, 

f35, f38, f48, f244, f83, f89, f74, f240, 

f23, f24, CCD) 

INSECT VENOMS 

3720 Allergy Profi le Insect Venoms 

(i1, i3, CCD) 

ATOPY, POLLEN-ASSOCIATED 

FOOD ALLERGIES 

3701 Allergy Profi le Atopy “Top Screen“ 

(rs1, rs2, fx5, fs52, CCD) 

3710 Allergy Profi le Atopy 

(g6, g12, t3, w6, d1, e1, e2, e3, m2, m6, f1, f2, 

f3, f4, f9, f14, f17, f31, f35, f49, CCD) 

3710 Allergy Profi le Atopy 3 

(g6, t3, t4, w6, d1, d2, e1, e2, e3, m2, m3, f1, 

f75, f2, f3, f4, f13, f14, f31, f49, CCD) 

3711 Allergy Profi le Pollen-Food 

Cross Reactions 

(g6, t3, w6, f4, f5, f13, f17, f20, f48, f89, 

f271, f275, f44, f49, f348, f237, f328, f31, 

f35, f85, CCD) 

3712 Allergy Profi le Pediatrics 

(gx, t3, w6, d1, d2, e1, e2, e3, m2, m3, m6, 

f1, f75, f2, f3, f76, f77, f78, e204, f4, f9, f14, 

f13, f17, f31, f35, f49, CCD) 

3713 Allergy Profi le Atopy “China“ 

(ts20, w1, w6, ds1, h1, e1, e2, i6, ms1, u80, f1, f2, 

f13, f14, f27, f88, fs33, fs34, f23, f234, CCD) 

3713 Allergy Profi le Atopy “China 3“ 

(ts22, w6, us1, ds1, es1, h1, ms5, f245, 

fs9, fs43, fs56, fs34, fs44, CCD) 


(ds1, h1, i6, e1, e2, ms1, ts20, u80, 

w1, w6, f1, f2, f13, fs33, CCD) 


(ds1, h1, i6, e1, e2, ms1, w1, w6, f1, f2, f13, 

f14, f23, f24, fs33, fs33, u80, CCD) 

3716 Allergy Profi le Atopy “Peru“ 

(e1, e2, e3, e7, e11, e82, e84, es172, i1, i3, i6, 

m1, m2, m3, m6, t18, u85, w29, w28, d1, d2, 

f75, f79, f1, f2, f23, f206, f13, f14, f104, f105, 

f26, fs32, f44, f49, CCD) 

EUROASSAY ALLERGY PROFILES 

3710 Allergy Profi le Inhalation 

(g1, g3, g6, g12, t2, t3, t4, t7, w1, w8, w6, w9, d1, d2, 

es4, e2, e3, e6, e1, e82, e84, m1, m2, m3, m6, CCD) 

3410 Allergy Profi le Food 

(f1, f75, f2, f78, f45, f4, f5, f9, f14, f10, f13, f17, f20, 

f84, f95, f237, f25, f31, f35, f85, f3, f23, f49, CCD) 

3712 Allergy Profi le Pediatrics/Atopy 

(g6, g12, t3, w6, d1, d2, e1, e2, e3, m2, m3, m6, 

f1, f75, f3, f2, f76, f77, f78, e204, f4, f9, f14, f13, 

f17, f31, f35, f49, CCD) 

Allercoat 6 System: Antibodies of class IgE against 600 different 

allergens of the areas animal allergens, environmental allergens, 

food, grasses, herbal and flower pollen, house dust, insects, mites, 

moulds, parasites, pharmaceutical drugs, trees. 

— 19 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

POD-labelled 

anti-human antibody 


antibody 

A 

B 

C 

D 

E 

F 

G 

H 

— 20 — 

substrate 

POD 

POD 

antigen-coated 

microplate well 

1 2 3 4 5 6 7 8 9 10 11 12 

EUROIMMUN Microplate ELISA 

stain 

chromogen 


• Polystyrene microplate strips coated with purified, biochemically characterized 

antigens are used as solid phase containing bound antigens. 


to the antigens coupled to the solid phase. 

• In a second step, the attached antibodies are detected with peroxidase-labelled 

anti-human antibodies. 

• In a third step, the bound antibodies are made visible using a chromogen/ 

substrate solution which is capable of promoting a color reaction. The intensity 

of the color produced is proportional to the concentration of antibodies in the 

serum sample. 

• Monospecific ELISA (enzyme immunoassays with a single antigen) provide a 

quantitative in vitro assay for the detection of antibodies. 

• “Profile ELISA” provide a semiquantitative in vitro assay for the detection of 

different antibodies on a single microplate strip. 

• The solid phase of “Pool ELISA” is coated with an antigen mixture for the semiquantitative 

detection of antibodies whose specificity must be subsequently 

investigated by monospecific assays. 

Reliable and Economical Calibration/Evaluation 

• In the case of a quantitative ELISA, calibration is generally performed using 

three cali bration sera. 

Calibration serum 1: upper limit of the measurement range 

Calibration serum 2: upper limit of the normal range (cut-off value) 

Calibration serum 3: negative 

• Only three wells are required for calibration, followed by serum samples. There 

is no need to incubate blank values or duplicate determinations. 

• Semiquantitative ELISA are performed using only one calibrator. Extended 

calibration curves are found in some ELISAs for immunity determination or CSF 

diagnostics. 

• The calibration is performed in relative units per milliliter (RU/ml) or, if an 

international reference serum exists, in international units per milliliter (IU/ml). 

• Each test can be optionally performed using a positive or negative control 

serum included in the test kit. Kit-specific reference ranges are provided for 

each calibrator and control serum. 

• All calibrations can be easily performed with the usual ELISA software. 

Easy, Quick and Economical Handling 

• Microplate strips containing break-off wells (except Profile ELISA). 

• To avoid mix-ups, microplate strips or reagent wells are printed with antigen 

abbreviations. 

• Reagents ready for use (wash buffer: concentrate). 

• Colour-coding allows clear identification of reagents. 

dark red: calibration serum 1 dark blue: pos. control serum 

red: calibration serum 2 green: neg. control serum 

light red: calibration serum 3 sample buffer and anti-human Ig PODconjugate: 

different colors 

• The sample buffer for infectious serology ELISA (detection of antibodies of class 

IgM) already contains an IgG/RF absorbent. 

• Compatible with all commercial washer and reader systems.



AG 

Determination of Low-Avidity Antibodies 

EUROIMMUN Microplate ELISA 

• An alternative principle for the serological diagnosis of fresh infections has been 

established by investigating the antibody avidity. 





• To identify low-avidity antibodies in a patient’s serum, two microplate ELISA 

are performed in parallel: one test is carried out in the conventional way, the 

other one includes urea treatment between incubations with patient’s serum 



• Low-avidity antibodies are present if the ELISA extinction is significantly reduced 

by urea treatment. For an objective interpretation, the relative avidity index (RAI) 

can be calculated out of the measured values with and without urea incubation. 

• Serum dilution 1 : 101, conjugate class anti-human IgG, POD-labelled. 

• 3-point calibration, quantitative (IgG). 

• The following test kits for avidity determination are available: Toxoplasma gondii, 

CMV, rubella virus, measles virus, VZV, TBE virus, West-Nile virus, EBV-CA. 

Antibody Determination in CSF 

• Indication: local infections of the brain. 

• CSF dilution 1 : 2, serum dilution 1 : 404. Conjugate classes anti-human IgG or 

IgM, POD-labelled. 

• Easy to conduct: ready-for-use reagents. 

• 4-point calibration, quantitative. Identical incubation conditions and times (room 

temperature; 60 min / 60 min / 15 min): all EUROIMMUN ELISA for CSF diagnostics 

can be combined without difficulty on one and the same micro plate. 

• The antibody concentration in the patient’s serum is determined in parallel to 

the antibody concentration in CSF on one and the same microplate. The CSF/ 

serum quotient CSQ is calculated from both measured values. 

path.-spec. 

• An intrathecal synthesis of specific antibodies is present if the CSF/serum 

quotient of the specific antibodies CSQ is significantly higher than the 

path.-spec. 

CSF/serum quotient of the whole IgG (CSQ ) or if necessary the CSQ . 

total lim. 

The relation of both values indicates the relative CSF/serum quotient CSQrel. (synonym: antibody specificity index, ASI). 

• Interpretation of results (according to the recommendations of Prof. Reiber): 

CSQ < 0,6: unreliable result, check for error 

rel. 

CSQ 0,6 – 1,3: standard range 

rel. 

CSQ 1,3 – 1,5: borderline range 

rel. 

CSQ > 1,5: Indication of pathogen-specific antibody production in the CNS 

rel. 

• For the automatic calculation of the CSQ EUROIMMUN provides a specific 

rel. 

Excel table free of charge. 

• Highest sensitivity, specificity and reproducibility. Antibody concentrations in 

serum and CSF can be determined over the total linear measurement range. 

• The following test kits for CSF diagnostics are available: Borrelia burgdorferi, 

Toxoplasma gondii, HSV-1, HSV-2, HSV-1/2 Pool, CMV, rubella virus, measles 

virus, mumps virus, VZV, TBE, EBV-CA. 

• All test systems for CSF diagnostics can also be used only for serology. 

• Perfectly adapted for the automated incubation in incubation devices. 

Number of Patients 

10 

8 

6 

4 

2 

RAI = E with urea 

E without urea 

0 

0 25 50 75 100 

Relative Avidity Index (RAI) in % 

Primary Infection 

Previous Infection 

Avidity of antibodies against EBV-CA (IgG) 

A CA 

B CB 

C CC 

D CD 

E 

F 

g 

h 

ELISA incubation scheme 

Table-based evaluation of the CSQ rel. 

CSQtotal 

1 2 3 4 5 6 

C1 

1:2 

S1 

1:404 

C2 

1:2 

S2 

1:404 

CA-D 

C3 

1:2 

S3 

1:404 

C4 

1:2 

S4 

1:404 

C5 

1:2 

S5 

1:404 

C6 

1:2 

S6 

1:404 

CSF- 

Calibrators C CSF S serum 

CSQalb. 

Reference range for normal values, 

intact blood-CSF barrier function 

Blood-CSF barrier dysfunction, 

no Ig production in CNS 

Blood-CSF barrier dysfunction, 

additional Ig production in CNS 

Clear Ig production in CNS, 

no disturbance in blood-CSF 

barrier function 

Error in blood extraction or analysis 

CFS/serum quotient diagram according to Reiber 

and Lange (1991) 

— 21 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

— 22 — 

ELISA Automation Using the EUROIMMUN Analyzers 

approved 

approved 

EUROIMMUN Analyzer I and EUROIMMUN Analyzer I-2P: Broad 

Parameter Spectrum, Proven Reliability, Variable Throughput 

• One for all: fully automated processing of all EUROIMMUN ELISA – autoimmune 

diagnostics, infectious serology and allergology – with only one system 

• Flexibility for your benefit: open system with more than 800 validated 

• 

EUROIMMUN parameters for serum, plasma and cerebrospinal fluid, over 50 or 

30 parameters in parallel. 

Convenient, simple and reliable operation: e.g. by scanning QC certificates using 

a 2D-hand barcode scanner – ready-for-use reagents and preprogrammed assay 

protocols enable you to start immediately. 

• Capacity and throughput: quick loading and efficient time management allow 

processing of up to 70 or 50 tests per hour – up to 7 or 3 plates, 180 or 144 

samples at the start of a run. 

• Security for patients: validated test systems and the comprehensive safety kit 

provide the basis for reliable diagnostics. 

• Reliability and service: instruments and reagents from one manufacturer, 

quick and targeted support from our personnel for a smooth workflow in your 

laboratory. 

Modular System: A Highly Sophisticated Solution 

• High convenience, fast and reliable loading through barcode identification of 

samples and reagents: automatic scanning when racks are inserted, reading of 

lot-specific QC data via 2D hand barcode scanner. 

• Dilution area: 288 or 192 dilution positions (Deepwell, 2 ml). 

• Liquid level detection (capacitive), multi-shot (dispensing) mode, automatic tip 

detection, clot detection. 

• Pipetting possible during plate transport due to separation of transport and 

pipetting unit. 

• 4 or 2 incubators with heating and shaking function, 4 or 3 incubators at room 

temperature. 

• Standard Windows software: familiar user interface, all relevant statistical 

functions provided, available in different languages. 

• Efficient use and convenient handling of tips and dilution plates through memory 

function. 

A Convincing and Reliable Package: EUROIMMUN Analyzer, 

EUROIMMUN ELISA, EUROIMMUN Service 

• Comprehensive test system validation for the EUROIMMUN Analyzer: all 

para meters validated in accordance with the 98/7.9/EC directive and based on 

EN ISO 13485:2003/CMDCAS. 

• All ELISA test systems are manufactured according to the European Quality 

Standards (IVD). 

• National and international conformity (standardisation): CE, IVD, FDA and 

CMDCAS. 

• Programming and set-up of automated system, including introduction to the 

system with customer training, performed by qualified personnel. 

• Reliable and fast delivery of consumables and reagents. 

• Connection to in-house computer system via communication protocol ASTM. 

• Maintenance contract with EUROIMMUN on request.



AG 

Pipette: 100 µl per well 


Wash: 300 µl wash buffer 

per well 




per well 




Incubating the Microplate ELISA 

Evaluate: photometric measurement 

at a wavelength of 450 nm 

microplate wells coated 

with antigens 

diluted 

samples 

enzyme 

conjugate 

chromogen/ 

substrate solution 

stop 

solution 

— 23 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

chromogen 

nRNP/Sm 

— 24 — 

stain 

Sm 

SS-A 

SS-B 

membrane coated 

with antigen 


antibody 

AP 

EUROASSAY: Line Blot in TITERPLANE Technique Format 

AP 

substrate 

AP-labelled 

anti-human 

antibody 

Scl-7.0 

Jo-1 

Control 

band 

EUROASSAY Anti-ENA ProfilePlus: detection of 

antibodies against SS-A and SS-B in a case of 

Sjögren’s syndrome. 


• Membrane strips coated with thin parallel lines of several purified, biochemically 

characterized antigens are used as solid phase. The membrane strips are fixed 

as BIOCHIPs in the fields of microscope slides. 



• In a second incubation step, the attached antibodies react with AP-labelled antihuman 

antibodies. 

• In a third step, the bound antibodies are stained with a chromogen/substrate 

solution which is capable of promoting a color reaction. An intense dark band 

at the line of the corresponding antigen appears if the serum sample contains 

specific antibodies. 

• The microscope slides are incubated using the TITERPLANE Technique: 

samples and reagents are applied to the reaction areas of a reagent tray. The 

slides are then placed into the recesses of the reagent tray, where all test strips 

of one slide come into contact with the liquids, and the individual reactions 

begin simultaneously. 

• Depending on the spectrum of antigens used, it is possible to analyze several 

antibodies next to each other and simultaneously under identical conditions. 

Easy Handling 

• Several serum samples can be analyzed simultaneously on one and the same 

slide. 

• Total time for performing the EUROASSAY test is about 100 minutes. During 

the washing procedure, reagents for the next incubation step can be applied to 

reagent trays. 

• All incubation steps proceed at room temperature. Shaking the slides together 

with the reagent tray on a circulatory shaker ensures the best possible 

sensitivity. 

• Low reagent consumption. Only 50 µl each of diluted serum and reagent are 

needed per test field. 

• Reagents ready for use (wash buffer: concentrate). 

Reliable and Simple Evaluation 

• Since results are evaluated visually, there is no investment required for 

photometers, etc. 

• The antigen bands are located at exactly defined positions, which means that 

evaluation of the test is much simpler than for Westernblots. 

• Correct completion of the individual incubation steps in each test field is 

indicated by staining of the control band. 

• Positive and negative results can be easily and reliably differentiated from each 

other. The intensity of the antigen bands correlates with the antibody titer. 

• The antigens used are highly pure, mostly isolated by affinity chromatography. 

The membrane strips do not contain any superfluous proteins which might 

cause unspecific positive results. 

• The incubated microscope slides can be stored for long periods. Results can be 

easily documented.



AG 

Incubating the EUROASSAY (TITERPLANE Technique) 

Pipette: 50 µl per field 

Incubate: 30 min shaking on a 

circulatory shaker 

(300 rpm) 


15 min cuvette 




(300 rpm) 


15 min cuvette 




(300 rpm) 

Wash: flush with deionized 

or distilled water, 

air dry 

Evaluate: visual assessment 

of color intensity 

slide 

membrane strips 

wash 

buffer 

wash 

buffer 

reagent tray 


enzyme conjugate 

chromogen/substrate 

solution 

— 25 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

— 26 — 

The EUROLINE: A New Technique for Extensive Antibody Profiles 

AP-labelled 

anti-human 

antibody 


antibody 

AMA M2 

M2-3E 

(BPO) 

Sp100 

PML 

gp210 

LKM-1 

LC-1 

SLA/LP 

Ro-52 

Control 

nRNP/Sm 

Sm 

SS-A 

Ro-52 

SS-B 

Scl-7.0 

PM-Scl 

Jo-1 

CENP B 

PCNA 

dsDNS 

Nucleos. 

Histones 

Rib. P-prot. 

AMA-M2 

substrate 

AP 


with antigen 

Control 

stain 

chromogen 

AP 

Mi-2 

Ku 

PM-Scl100 

PM-Scl7.5 

Jo-1 

SRP 

PL-7. 

PL-12 

EJ 

OJ 

Ro-52 

Control 

Incubated EUROLINE test strips (Autoimmune 

Liver Diseases Profile, ANA Profile 3, Myositis 

Profile 3. 


• Membrane strips coated with thin parallel lines of several purified, biochemically 

characterized antigens are used as solid phase. The membranes are fixed as 

BIOCHIPs onto synthetic foil. 



• In a second incubation step, the attached antibodies react with alkalinephosphatase-labelled 

anti-human antibodies. 





• Depending on the spectrum of antigens used, it is possible to analyze several 

antibodies next to each other and simultaneously under identical conditions. 

Easy Handling, Reliable and Simple Evaluation 

• A separate membrane strip is incubated for each serum sample. 

• Total time for performing the analysis is about 105 minutes. 

• The incubation can be automated using the EUROBlotMaster. 

• All incubation steps proceed at room temperature. 

• The antigen bands are located at exactly defined positions, which means that 

the evaluation of the test is much simpler than for Westernblots. 

• Correct completion of the individual incubation steps is indicated by staining of 

the control band on each EUROLINE test strip. 

• Positive and negative results can be easily and reliable differentiated from each 

other. The intensity of the antigen bands correlates with the antibody titer. 

• The antigens used are highly pure, mostly isolated by affinity chomatography. 

The membrane strips do not contain any superfluous proteins which might 

cause unspecific positive results. 

• The incubated EUROLINE test strips can be stored for long periods. Results can 

be easily documented. 

• The program EUROLineScan from EUROIMMUN has been developed to enable 

quantitative evaluation of EUROLINE test strips, to facilitate management of 

data, and to provide detailed documentation of results. First, the incubated 

EUROLINE test strips are scanned using a flatbed scanner. EUROLineScan 

recognizes the position of the strips, even if they have been placed inexactly, 

identifies the bands, and measures their intensity. The results are then saved 

together with the image data. A separate results sheet can be produced for each 

patient.



AG 

EUROLINE Automation Using EUROBlotMaster and EUROLineScan 

EUROBlotMaster 

• Standardisation of immunoblot strips – higher precision and reproducibility. 

• Automatisation of all EUROIMMUN immunoblot strips (EUROLINE, EUROLINE- 

WB, Westernblot). 

• Over 90 validated profiles available (autoantibody diagnostics, infectious 

serology and allergology). 

• Two models available: for up to 30 or 44 strips per test run. 

• Easy operation. 

• Combination of different conjugates/tests in one run. 

• Walk-away function – fully automated from the start to the end of processing 

following loading. 

• Compatible with modern evaluation systems such as EUROBlotCamera and 

EUROLineScan. 

Automatic Evaluation of the Results Using EUROLineScan 

• For all EUROIMMUN blot systems: EUROLINE, EUROLINE-WB, Westernblot. 

• For all areas: autoimmune diagnostics, infectious serology and allergology. 

• EUROBlotCamera: digitalisation of strips while in the incubation tray. 

• EUROBlotScanner: digitalisation of strips using flatbed scanner. 

• Fully automated identification, quantitation and assignment of bands. 

• Option to modify results (changes are automatically documented). 

• Complete results obtained just a few minutes after finishing the incubation. 

• Fully automated administration and documentation of extensive individual data. 

• Electronic archiving of all images and data (avoids the need to store potentially 

infectious blot strips). 

• Online connection to laboratory software. 

• Network compatible. 

EUROBlotMaster 

EUROBlotCamera EUROBlotScanner 

— 27. — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

Westernblot/EUROLINEWB: Reliable Differentiation of Antibodies Present 

— 28 — 

AP-labelled 

anti-human 

antibody 


antibody 

EUROLINE-WB Borrelia 

substrate 

AP 

p 83 

p 41, Flag. 

p 39, Bmp A 

p 31, Osp A 

p 30 

p 25, Osp C 

p 21 

p 19 

p 17. 

AP 


with antigen 

stain 

Alignment bar 

Control band 

chromogen 

VlsE antigen 

on EURO LINE 

membrane chip 

EUROLINE-WB: detection of antibodies against 

Borrelia. 


• Membrane strips containing electrophoretically separated antigen extracts are 

used as solid phase. The position of the proteins depends on their respective 

molecular masses. 


to the antigens coupled to the membrane. 

• In a second incubation step, the attached antibodies react with AP-labelled antihuman 

antibodies. 





• Evaluating the band patterns on the incubated membrane strips involves 

differentiating non-specific from specific antibodies. The number and intensity 

of the specific bands is decisive for the result “positive/negative“. 

Easy Handling, Reliable Evaluation and High Diagnostic Significance 

• A separate membrane strip is incubated for each serum sample. 

• Total time for performing the Westernblot test is about 115 minutes. 

• All incubation steps proceed at room temperature. 

• The bands are assigned according to a lot-specific evaluation matrix provided. 

A separate lot is issued for each electropho resis gel, helping to avoid errors in 

the assignment of the bands. 

• Every test kit contains a membrane strip of the same lot incubated with a 

positive reference serum. Therefore, there is no need to incubate a positive 

control serum. 

• The membrane strips are pre-numbered to prevent confusion. Laborious 

labelling is not necessary. 

• Correct completion of the individual incubation steps for each membrane strip 

is indicated by staining of the control band at the bottom of the strip. 

• Positive and negative reactions can be easily and reliably differentiated from 

each other. The intensity of the antigen bands correlates with the antibody titer. 

• The Westernblot is the method of choice when the objective is to confirm or 

differentiate positive results obtained in a screening test (indirect immunofluorescence 

or microplate ELISA). 

• EUROLINE-WB is a combination of westernblot and line blot techniques. Proteins 

from a whole antigen extract are electrophoretically separated according to 

molecular mass and transferred onto a nitrocellulose membrane. Highly purified 

native or recombinant antigens are then printed as lines onto the westernblot 

strips (EUROLINE membrane chip). 

• The program EUROLineScan from EUROIMMUN has been developed to enable 

quantitative evaluation of Westernblot/EUROLINE-WB test strips, to facilitate 

management of data, and to provide detailed documentation of results. First, 

the incubated Westernblot/EUROLINE-WB test strips are scanned using a flatbed 

scanner. EUROLineScan recognizes the position of the strips, even if they have 

been placed inexactly, identifies the bands, and measures their intensity. The 

results are then saved together with the image data. A separate results sheet 

can be produced for each patient.



AG 

Incubating the EUROLINE/Westernblot/EUROLINEWB 

using the EUROBlotMaster or manually on a rocking platform 

Pipette: 1.5 ml per channel 

Incubate: 5-15 min shaking, depending 

on test system 

Aspirate off: 


Incubate: 30 min shaking 

Wash: 1.5 ml buffer, 

5 min incubation, 

aspirate off 



Wash: 1.5 ml buffer, 

5 min incubation, 

aspirate off 



Wash: rinse with distilled 

water, aspirate off 

Evaluate: with EUROLineScan or 

visual assessment 

membrane strip 

incubation channel 

buffer 


buffer 

enzyme conjugate 

buffer 

chromogen/substrate solution 

Applicable for most EUROLINE/Westernblot/EUROLINE-WB test kits 

— 29 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

— 30 — 

The EUROArray: DNA Microarray Test Systems for Diagnostics (IvD) 

Blood sample DNA isolation 

Patient DNA 

DNA contains target sequence 

Primer 

1 st PCR cycle 

2 nd PCR cycle 

Next cycles 

Exponential DNA amplification 

and fluorescence labelling 

Binding of PCR products to 

complementary DNA probes 

of the microarray 

Carrier material DNA spots 

DNA does not contain target sequence 

Primer 

1 st PCR cycle 

2 nd PCR cycle 

Next cycles 

No DNA amplification 

No binding without 

complementary PCR products 

Carrier material DNA spots 

EUROArray slide and BIOCHIP after incubation. 


Sample Preparation 

• DNA isolation: In order to investigate with a microarray if a patient‘s DNA 

contains particular sequences, the DNA must first be extracted from the patient‘s 

blood. This is performed, for example, using DNA isolation kits. 

Amplification of Patient DNA: Polymerase Chain Reaction (PCR) 

• The sections of DNA to be investigated are amplified million-fold using the 

polymerase chain reaction (PCR). 

• Two starter DNA molecules (primers) define the region to be copied. If the 

patient DNA contains the corresponding section (target sequence), the primers 

bind and the target sequence is copied. 

• This reaction is repeated many times, so that the DNA region between the 

primers is greatly (exponentially) amplified. 

• The resulting PCR products are labelled with a fluorescent dye, which enables 

them to be detected subsequently by the microarray. If the target sequence is 

not present in the patient sample, then the primers cannot bind and the DNA is 

not amplified. 

Analysis of PCR Products on the Microarray: DNA Microarray Hybridisation 

• The PCR products are incubated with the microarray. 

• They are fi rst mixed with a hybridisation buffer, which provides optimal 

conditions for binding of the PCR products to the complementary probes on 

the microarray. 

• This binding is measured via the fl uorescence signals emitted by the spots. 

Advantages of the EUROArray System 

• Array platform based on proven BIOCHIP Technology. 

• Ready-to-use PCR components. 

• Simple procedure. 

• Standardised incubation using established TITERPLANE Technique. 

• Integrated control reactions secure sensitivity and specificity for every test 

sample. 

• Fully automated standardised evaluation, interpretation and archiving of results 

(EUROArrayScan software). 

• No DNA isolation with EUROArray Direct: the analysis is performed directly 

from pretreated blood. 

• Complete process from receipt of samples to issuing of results is IVD validated 

and CE labelled (DNA extraction, test kits, microarray scanner, software). 

• Pre-prepared LIMS connection.



AG 

Performance and Evaluation of the EUROArray Test 

Save Time and Money with the “EUROArray Direct“ Procedure 

• For some parameters EUROIMMUN offers a rapid procedure in which DNA 

isolation is not necessary. 

• The blood sample is incubated with extraction solution provided in the kit (E 1 

and E 2, see figure). The DNA extract is used directly in the PCR. 

Comparison EUROArray EUROArray Direct 

Blood volume ~ 200 µl 5 µl 

Time DNA isolation: DNA extraction: 

approx. 80 min for 40 samples < 20 min. for 40 samples 

Costs For DNA isolation kit No additional costs, extraction 

solutions contained in the kit 

Simple, uncomplicated and effortless 

• All PCR reagents supplied in EUROArray kits are ready for use, including the 

DNA polymerase and the validated specific primers. Thus, the number of 

pipetting steps is reduced to a minimum and laborious optimisation processes 

are eliminated. 

• The PCR works reliably with minimal effort: the pre-prepared PCR reagents are 

simply combined, and the DNA is then added to this master mix. 

• The DNA microarray hybridisation is performed under exact, standardised 

conditions using the proven TITERPLANE Technique. This procedure is simple 

and reliable. The samples (PCR products + hybridisation buffer) are pipetted 

onto the reaction fields of a reagent tray. The slides are then placed into the 

recesses of the reagent tray, whereby all BIOCHIPs come into contact with the 

liquids simultaneously. Thanks to the hydrophobic surroundings, the fluid drops 

remain stable on the hydrophilic reaction fields during the incubation and do not 

run into one another. 

• After a one-hour incubation period in the hybridisation station, the EUROArray 

slides are washed: 10 slides are processed in just 5 minutes and can then be 

evaluated. 

Fully automated standardised evaluation delivers fast and reliable 

results 

• With the EUROIMMUN Microarray Scanner and EUROArrayScan software, 

EUROArrays are evaluated easily, quickly and objectively without the need to 

study complicated manuals. 

• EUROArrayScan software can be integrated into EUROLabOffice and other 

laboratory information management systems (LIMS) without any difficulties. 

• At the start of each run, the data for the samples to be examined are entered 

and are then transferred automatically into the working list by the software. 

• After the incubated slides have been placed into the microarray scanner, the 

scanning procedure is initiated simply by a mouse click. 

• EUROArrayScan software evaluates all data fully automatically, produces a 

report and documents and archives all results. 

• Results for a EUROArray slide (up to five samples) are obtained in less than 20 

seconds! 

5 µl Blood 

To be used 

directly for PCR 

Pipette samples 

Reagent tray 

Incubate 

20 µl E1 

5 sec 

1 min 

20 µl E2 

DNA extraction with the „Direct procedure”. 

+ 

Ready for use 

PCR reagents PCR master mix 

PCR 

Place slide onto tray 

1 hour 

Hybridisation station with four 

EUROArray slides 

— 31 — 

Investigation 

Techniques



AG 

Investigation 

Techniques 

125 I 

— 32 — 

radioactively 

labelled 

antigen 

(“tracer”) 

solid phase 

(tube surface) 

EUROIMMUN Radioimmunoassays (RIA/IRMA) 

precipitation 

agent 

antibody 

specific human antibody 

radioactively 

labelled 

antibody 

analyte 

125 I 

125 I 

Test principle RIA (precipitation techniques) 

• In the first incubation step patient sera are incubated with 125 I-labelled antigen in 

polystyrene tubes. Any specific antibodies in the sera bind to the antigen. 

• In the second incubation step the antigen-antibody complexes are precipitated 

using a precipitation agent. 

• The precipitate is washed with buffer. After centrifugation and decanting of 

the supernatant, the radioactivity in the precipitate is counted using a gamma 

counter. The intensity of the radioactivity is proportional to the concentration of 

specific antibody in the patient serum. 

• The antibody concentration is evaluated quantitatively using a calibration curve. 

Test principle RIA (coated tubes) 

• RIA tests (coated tubes) are competitive ligand assays for antibody and antigen 

determinations. 

• The intensity of radioactive radiation is inversely proportional to the concentration 

of specific antibodies or antigens in the sample. 

• The quantitative evaluation of the antigen/antibody concentration is carried out 

using a calibration curve. 

Test principle IRMA (antigen determination) 

• With this test principle, monoclonal antibodies which are bound directly or 

indirectly to the inner wall of polystyrene tubes are used. 

• During the first incubation step, the patient sera to be investigated are incubated 

with the monoclonal 125I-labelled antibodies in the coated tubes. 

• The antigen in the sample is bound by the immobilised antibodies and by the 

125I-labelled antibodies. This results in a solid-phase bound sandwich complex. 

• The unbound 125I-labelled antibodies are removed by washing and subsequently 

decanting. The intensity of radioactive radiation is proportional to the concentration 

of antigens in the patient serum. 

• The quantitative evaluation of the antigen concentration is carried out using a 

calibration curve. 

Simple and economical handling, reliable analysis 

• Simple test procedure. 

• Synchronous processing of samples, including different tests in parallel. 

• Ready-to-use reagents (possible exceptions: tracer, precipitation reagents). 

• Different test formats for small and large sample series. 

• Because of the large measurement range of EUROIMMUN RIA, further 

• 

measurements with other sample dilutions are generally not necessary. 

Simple evaluation of test results. 

• Each test can be optionally evaluated with controls which are supplied in the 

test kit. Test kit-specific reference ranges are given for all controls. 

• EUROIMMUN radioimmunoassays show the following analytical characteristics: 

– High analytical specificity. 

– High detection sensitivity. 

– High clinical sensitivity and specificity. 

– Good reproducibility.



AG 

EUROIMMUN PRODUCTS FOR ThE DETERMINATION OF AUTOANTIBODIES 

— 33 — 

EUROIMMUN Products for the 

Determination of Autoantibodies



AG 


Determination of Autoantibodies 

EUROPLUS ANA Mosaic 20A (HEp-20-10 cells, 

pri mate liver, SS-A+SS-B BIOCHIPs, rib. P-prot.+ 

Jo-1 BIOCHIPs: antibodies against SS-A/SS-B. 

Order No. Formats 

FA 1512-####-20 page 127. 

HEp-2010: antibodies against spindle fibers. 


FA 1522-#### page 128 

Incubated EUROASSAY Anti-ENA ProfilePlus. 


DA 1590-####-1 G page 80 

— 34 — 

Autoantibodies against Cell Nuclei (ANA) 

Indirect Immunofluorescence Test: EUROPLUS ANA Mosaic 20A 

• Screening test for the detection of antibodies against cell nuclei (ANA). 

• Indications: rheumatic diseases. 

• Initial dilution 1 : 100; conjugate class anti-human IgG, FITC-labelled. 

• Using HEp-20-10 cells many antibodies against cell nuclei can be analyzed, e.g. 

anti bodies against DNA, histones, RNA, nRNP, Sm, SS-A, SS-B, nuclear dots, 

centro meres, nuclear membrane, nucleoli (PM-Scl, fibrillarin, RNA polymerase 

I, NOR), Scl-7.0, cyclin I and II, spindle fibers, midbody, centrioles. 

• In addition, cytoplasmic autoantibodies are identified with HEp-20-10 cells: antibodies 

against ribosomes, Jo-1, mito chondria, Golgi apparatus, actin etc. 

• The primate liver permits the verification of results between both substrates, makes 

the pre-differentiation of a large number of ANA possible, and helps to establish 

titer levels. Moreover, the primate liver often contains additional antigens, 

allowing the identification of further autoantibodies: antibodies against LMA, LSP, 

endo mysium, bile ducts and endothelium cells, as well as cANCA und pANCA. 

• The EUROPLUS system is a monospecific test that can be used to confirm the 

presence of autoantibodies against cell nuclei and cytoplasm with one and the 

same test kit. The following antigens are currently available as EUROPLUS 

BIOCHIPs: SS-A, SS-B, nRNP/Sm, Sm, Scl-7.0, Jo-1, ribosomal P-proteins. 

Indirect Immunfluorescence Test: Innovative Cell Line HEp-20-10 

with a high number of mitotic cells 

• Screening test for detection of antibodies against cell nuclei. 



• Compared to standard HEp-2 cells, HEp-20-10 cells demonstrate 10-fold more 

mitotic cells. Antibodies against mitotic-specific structures (centromeres, spindle 

fibers, midbody, centrioles, NOR) can be more easily identified than with conventional 

preparations. 

• At the same time, the cell line HEp-20-10 offers the full antigen spectrum for cell 

nuclei antibody diagnostics. 

• The BIOCHIP with HEp-20-10 can be supplemented with additional substrates, 

for example, primate liver (ANA; Order No. FA 1512-####-1) as well as rat kidney 

and rat stomach (Order No. FA 1802-####-3). 

EUROASSAY: Anti-ENA ProfilePlus 

• Differentiation of anti-nuclear antibodies (ANA). 


• Serum dilution 1 : 100; conjugate class anti-human IgG, AP-labelled. 

• 6 relevant anti-nuclear antibodies against “extractable nuclear antigens“ (ENA) 

can be detected simultaneously and monospecifically: antibodies against 

nRNP/Sm, Sm, SS-A, SS-B, Scl-7.0, Jo-1. 

• Native antigens, purified by affinity chromatography. 

• On request EUROASSAY can be produced with special antigen combinations, 

for example, with dsDNA, histones, nucleosomes, PM-Scl, nRNP/Sm, Sm, SS-A, 

Ro-52, SS-B, Scl-7.0, Jo-1, riboso mal P proteins, centromere protein B, M2, M4, 

M9, SLA/LP, LC-1, LKM-1.



AG 

EUROLINE: ANA Profile 3 

• Differentiation of antibodies against cell nuclei (ANA). 

• Indications: Sharp syndrome (MCTD), systemic lupus erythematosus, Sjögren’s 

syndrome, systemic sclerosis, poly/dermatomyositis, PBC. 


• With the EUROLINE ANA-Profile 3, fifteen autoantibodies can be determined: 

anti bodies against nRNP/Sm, Sm, SS-A, Ro-52, SS-B, Scl-7.0, PM-Scl, Jo-1, centromere 

protein B, PCNA, dsDNA, nucleosomes, histones, ribosomal P-proteins, 

AMA M2. 

• Antibodies against SS-A are characteristic markers for SLE and Sjögren’s 

syndrome. In contrast, antibodies against Ro-52 also occur in patients with other 

autoimmune diseases. 

• Native antigens, purified by affinity chromatography (exception: centromere 

protein B, PM-Scl, Ro-52, PCNA). 

• Further antigen combinations: page 80. 

• Test strips can be automatically incubated and evaluated using the systems 

EUROBlotMaster und EUROLineScan (see page 27.). 

EUROLINE: Myositis Profile 3 

EUROLINE: Systemic Sclerosis Profile (Nucleoli) 


• Differentiation of myositis-associated antibodies against cell-nuclear and 

• 

cytoplasmic antigens. 

Indications: poly/dermatomyositis. 

• Serum dilution 1 : 100, conjugate class anti-human IgG, AP-labelled. 

• With the EUROLINE Myositis Profile 3, eleven autoantibodies can be determined: 

anti bodies against Mi-2, Ku, PM-Scl100, PM-Scl7.5, Jo-1, SRP, PL-7., PL-12, EJ, OJ 

and Ro-52. 



• Differentiation of systemic sclerosis-associated antibodies against cell-nuclear 

antigens. 

• Indications: systemic sclerosis (SSc, diffuse and limited form), overlap syndromes. 


• With the EUROLINE Systemic Sclerosis Profile (Nucleoli), thirteen autoantibodies 

can be determined: anti bodies against Scl-7.0, CENP A, CENP B, RP11 (RNAP-III), 

RP155 (RNAP-III), fibrillarin, NOR-90, Th/To, PM-Scl100, PM-Scl7.5, Ku, PDGFR, 

Ro-52. 



nRNP/Sm 

Sm 

SS-A 

Ro-52 

SS-B 

Scl-7.0 

PM-Scl 

Jo-1 

CENP B 

PCNA 

dsDNA 

nucleos. 

histones 

rib. P-prot. 

AMA M2 

control 

Incubated EUROLINE ANA Profile 3. 


DL 1590-1601-3 G page 82 

Mi-2 

Ku 

PM-Scl100 

PM-Scl7.5 

Jo-1 

SRP 

PL-7. 

PL-12 

EJ 

OJ 

Ro-52 

control 

Incubated EUROLINE Myositis Profile 3. 


DL 1530-1601-3 G page 82 

Scl-7.0 

CENP A 

CENP B 

RP11 (RNAP-III) 

RP155 (RNAP-III) 

fibrillarin 

NOR-90 

Th/To 

PM-Scl100 

PM-Scl7.5 

Ku 

PDGFR 

Ro-52 

control 

Incubated EUROLINE Systemic Sclerosis Profile 

(Nucleoli). 


DL 1532-1601 G page 82 

— 35 — 





AG 



Incubated ELISA ANA Screen (antigen mixture of 

dsDNA, histones, nRNP/Sm, Sm, SS-A, SS-B, Scl- 

7.0, Jo-1, riboso mal P-proteins, centro mere). 


EA 1590-9601-8 G page 89 

Incubated ELISA Anti-ENA ProfilePlus 2 (antigens: 

riboso mal P-proteins, nRNP/Sm, Sm, SS-A, SS-B, 

Scl-7.0, Jo-1, centro mere). 


EA 1590-1208-2 G page 89 

Incubated ELISA Anti-SS-A, Anti-SS-B. 


EA ####-9601 G page 89 

— 36 — 


Microplate ELISA: ANA Screen, Anti-ENA PoolPlus 

• Screening test for predifferentiation of antibodies against cell nuclei (ANA) and 

cytoplasm components. 


syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis. 


• One microplate well incubated per patient. 

• 1-point calibration, semiquantitative. 

• Native antigens (exception: centromere, recombinant). 

• The ANA Screen ELISA supplements the gold standard immunofluorescence. 

It is based on a mixture of 10 highly purified antigens, which provide higher 

sensitivity and specificity than the undefined cell extracts used by other 

manufacturers. 

• Two ELISAs with different antigen combinations, adapted to particular indications 

or for follow-up of immunofluorescence patterns, are available. 

Microplate ELISA: SLE Profile 1/2, Anti-ENA ProfilePlus 1/2 

• Differentiation of antibodies against cell nuclei (ANA) and cytoplasm components. 


syndrome, progressive systemic sclerosis, polymyositis/dermatomyositis. 

• Serum dilution 1 : 200; conjugate class anti-human IgG, POD-labelled. 

• 8 or 6 relevant antibodies can be detected simultaneously. 

• 1-point calibration, semiquantitive. Calibrator pool and negative controls each 

on a separate microplate strip (SLE Profiles and Anti-ENA ProfilePlus 2) or on 

the same microplate strip as the patient serum. 

• Native antigens (exception: Ro-52, centromere and PM-Scl, recombinant). 

• In total 4 different ELISAs with different antigen combinations, adapted to 

particular indications or for follow-up of immunofluorescence patterns, are 

available. 

Microplate ELISA: ANA Single-Antigen ELISAs 

• Differentiation of antibodies against cell nuclei (ANA) and cytoplasm components. 



• Antibodies against cell nuclei components can be determined quantitatively in 

RU/ml. 

• 3-point calibration, quantitative. 

• Identical incubation conditions and times: all single-antigen tests can be combined 

with each other on one microplate. 

• Native antigens (exceptions: centromere and PM-Scl, recombinant). 

• Single-antigen ELISAs available for detection of antibodies against cell nuclei 

and cytoplasm antigens: ssDNA, nucleosomes, dsDNA, histones, ribosomal P 

proteins, PM-Scl, nRNP/Sm, Sm, SS-A, SS-B, Scl-7.0, Jo-1, centromere.



AG 

Indirect Immunofluorescence Test: Crithidia luciliae 

• Detection of antibodies against dsDNA. 

• Indication: lupus erythematosus disseminatus. 

• Initial dilution: 1:10, conjugate class anti-human IgG, FITC-labelled. 

• Animal pathogenic haemoflagellates of Crithidia luciliae are used for the detection 

of autoantibodies against double-stranded, native DNA (dsDNA, nDNA) 

with indirect immunofluorescence. These protozoa possess a giant mitochondrion 

containing dsDNA (kinetoplast) that, in general, does not show any of the 

other antigens present in the cell nuclei. Antibodies reacting with the kinetoplast 

are therefore only directed against dsDNA. 

• Alongside the conventional CLIFT, which shows a particularly high disease 

specificity, EUROIMMUN has developed an Anti-Crithidia luciliae sensitive IFT 

(order no. FA 157.2-####-1), which is comparable in sensitivity to the Anti-dsDNA- 

NcX ELISA and the Farr assay. However, despite comparable sensitivities, the 

assays identify different patients. To increase the serological hit rate different 

test systems are often combined. 

Microplate ELISA: Anti-dsDNA-NcX 

• Monospecific detection of antibodies against dsDNA. 

• Indication: lupus erythematosus disseminatus. 

• Serum dilution 1: 200, conjugate class anti-human IgG, POD-labelled. 

• Antibodies against dsDNA can be determined quantitatively in IU/ml. 


• Antigen: double-stranded DNA, complexed with nucleosomes (NcX). 

• Due to good sensitivity and specificity, the Anti-dsDNA-NcX ELISA stands out 

by high diagnostic efficiency. High concentrations of autoantibodies against 

dsDNA in the ELISA are considered to be a reliable marker for the diagnosis 

or prognosis of SLE. Individual changes in the dsDNA antibody concentration 

correlate with the activity of the disease and can be used for monitoring the 

development of the disease in SLE patients. In cases of immunosuppressive 

therapy or clinical remission dsDNA antibodies cannot be detected with the 

ELISA anymore. 

Anti-dsDNA RIA by Farr 

Autoantibodies against DoubleStranded DNA (dsDNA) 

• Monospecific detection of antibodies against dsDNA. 

• ndication: lupus erythematosus disseminatus. 

• Use of undiluted samples. 

• Antigen: 125I-labelled dsDNA from plasmid DNA. 

• The Farr radioimmunoassay has always been of great importance. On the 

whole, it has the same specificity as the immunofluorescence test and the same 

sensitivity as the ELISA. Apparently, its well-known high diagnostic efficiency 

is based on the fact that only the fraction of the anti-dsDNA antibodies which 

is able to form bigger precipitating immune complexes with circulating DNA in 

liquid phase contributes to the measuring signal. The principle of the Farr test 

reflects, so to speak, the significant step in the pathomechanism of SLE: the 

formation of appropriate immune complexes, deposits of which build up in the 

joints, kidneys, liver and other organs. 

Crithidia luciliae: antibodies against dsDNA. 


FA 157.2-#### page 128 

Incubated ELISA Anti-dsDNA-NcX. 


EA 157.2-9601 G page 89 

RIA Anti-dsDNA. 


RA 157.1-10001 page 91 

— 37. — 





AG 



Incubated ELISA Anti-CCP, Anti-Sa. 

Order No. (Anti-CCP) Formats 

EA 1505-9601 G page 89 

— 38 — 

EUROIMMUN 

M edizinische 


AG 

Antibodies against cyclic citrullinated peptides (CCP): 

An ELISA for specifi c diagnosis of rheumatoid arthritis 

H 

N 

O 

NH 

H 2N + NH 2 

Autoantibodies against CCP and Sa 

Peptidylargininedeiminase 

(PAD) 

Ca 2+ 

H 

N 

NH 

O NH 2 

L-arginine L-citrulline 

peroxidase-labelled 

anti-human antibody 

colourless 

chromogen 

The amino acid citrulline Principle of the anti-CCP ELISA 

Rheumatoid arthritis (RA) is one of the 

most common autoimmune diseases, affecting 

around 1% of the world population. It is 

characterised by infl ammation of the synovial 

membrane, which spreads symmetrically 

from the small to the large joints. Initial 

symptoms include painful swelling of fi nger 

joints with morning stiffness in the joints. 

Early diag nosis and immediate commencement 

of suitable therapy is necessary to 

keep the disease under control. 

The most commonly performed serological 

test in suspected RA cases was until now the 

determination of rheumatoid factors (RF). 

These are antibodies (predominantly of class 

IgM) which react with gamma globulins and 

occur in 60-80% of RA patients. RF are a sensitive 

but not very specifi c marker for RA, 

since they also occur in healthy individuals 

and in patients with various infections or 

other autoimmune diseases (systemic lupus 

erythematosus, Sjögren’s syn drome, scleroderma 

and others). 

40-60% of RA patients also exhibit autoanti 

bodies against epidermal fi l ag grin 1 (RA 

keratin, anti-pe ri nu clear fac tor) in their serum. 

Fil ag grin is a protein of the epi dermis, 

which links keratin fi laments to one another. 

Autoanti bodies against fi laggrin are detected 

by indirect immuno fl uor escence: the antigen 

substrate rat oesophagus shows staining of 

the stratum corneum (RA keratin) on the 

luminal side; anti-perinuclear factors (APF) 

are apparent in the cyto plasmic inclusion 

bodies of human epithelial cells of the oral 

mucosa. 

O 

Microplate ELISA: Anti-CCP, Anti-Sa 

• Screening test for the specific determination of autoantibodies against cyclic 

citrullinated peptides (CCP) and citrullinated Sa. 

• Indication: rheumatoid arthritis (RA). 


• Antibodies against CCP and Sa can be determined quantitatively in RU/ml. 

Optional reference control for the determination of ratio values. 

• Antigen: synthetic cyclic citrullinated peptides (CCP, second generation), 

citrullinated Sa. 

Antigen Order No. 

CCP EA 1505-9601 G 

Sa EA 151a-4802 G 

EUROIMMUN AG · 23560 Luebeck (Germany) · Seekamp 31 · Telephone +49 451 58550 · Fax 5855591 · E-mail euroimmun@euroimmun.de · www.euroimmun.com 

POD 

POD 

stain 

human antibody 

against CCP 

synthetic CCP 

In recent years it has been shown that the 

rare amino acid citrulline, which is present in 

fi laggrin, is a substantial component of the 

antigenic epitope. Enzyme immunoassays 

which use synthetic citrullinated peptide 

as the target antigen offer a useful alternative 

to indirect immunofl uorescence 2 . A 

direct comparison study demonstrated that 

the sensitivity can be increased from 49% 

to 68% by using cyclic citrullinated peptide 

instead of linear citrullinated peptide as an 

ELISA substrate 3 . Antibodies against cyc li c 

citrulli nated pep tides (CCP) are a new and 

highly specifi c marker for RA. 

An ti bodies against CCP are predominantly 

of class IgG and have a specifi city of 98% 

for RA. They are observed very early in the 

disease course and have a high predictive 

value: patients with anti-CCP antibodies 

develop signifi cantly more radiologically 

detectable joint damage than anti-CCPnegative 

patients 4 . Antibodies against CCP 

possess a much higher specifi city than RF 

(anti-CCP: 97%, RF: 62%) with the same sensitivity 

(anti-CCP: 79%, RF: 78%) 5 . They can 

be detected in early stages of the disease in 

79% of patients. 

EU ROIMMUN offers an innovative microplate 

ELISA for quantitative deter min ation of 

autoantibodies against CCP. Diluted patient 

sera are incubated in wells coated with synthetic 

cyclic citrullinated peptides (second 

gener ation). Specifi c antibodies in the serum 

bind to the immobi lised antigen and cause a 

photo metric colour reaction by means of an 

enzyme-coupled secondary antibody. Five 

Anti-CCP ELISA 

calibration sera ensure reliable measurement 

of antibody concentrations. The EURO- 

IMMUN Anti-CCP ELISA is a highly specifi c 

and sensitive sero logical test system for the 

diagnosis of RA. 

Panel n 

Anti-CCP 

positive 

Sensitivity RA 419 329 (78.5%) 

Asymptomatic blood 

donors 

400 2 (0.5%) 

Psoriatic arthritis 28 0 

Other arthritides 35 3 (8.6%) 

Systemic lupus 

erythematosus 

108 3 (2.8%) 

Sjögren‘s syndrome 106 2 (1.9%) 

Scleroderma 98 3 (3.1%) 

Autoimmune 

thyroiditis 

Wegener‘ 

granulomatosis 

Anti-parvovirus B19 

positive 

159 4 (2.5%) 

25 1 (4.0%) 

126 3 (2.4%) 

Viral hepatides 54 0 

Anti-HIV positive 5 0 

Tuberculosis 10 0 

Specifi city RA 1154 21 (98.2%) 

1) Nogueira et al., Ann. Rheum. Dis. 60: 882 (2001) 

2) Schellekens et al., J. Clin. Invest. 101: 273-281 (1998) 

3) Schellekens et al., Arthritis Rheum. 43: 155-163 (2000) 

4) Kroot et al., Arthritis Rheum. 43: 1831-1835 (2000) 

5) Vasishta, Am. Clin. Lab. 21: 34-36 (2002)



AG 

Autoantibodies against Mitochondria (AMA) 

Indirect Immunofluorescence Test: EUROPLUS Rat Kidney and 

M2 BIOCHIPs 

• Screening test for the detection of antibodies against mitochondria (AMA) including 

simultaneous confirmation of the subtype AMA M2. 

• Indication: primary biliary cirrhosis (PBC). 

• Initial dilution 1 : 100; polyvalent conjugate anti-human IgAGM, FITC-labelled. 

• Rat kidney is the standard substrate for detecting anti-mitochondrial antibodies. 

Nine AMA types (M1 to M9) can be differentiated. 

• The BIOCHIP coated with M2 permits monospecific confirmation of antibodies 

against the native pyruvate dehydrogenase complex and the recombinant M2 

fusion protein (BPO) in one single test procedure, thus a PBC can be diagnosed 

serologically with con fidence. 

• This BIOCHIP Mosaic can be supplemented as required using additional 

substrates, e.g. HEp-2 cells (ANA, nuclear dots), rat liver (liver-kidney microsomes, 

LKM) or rat stomach (ASMA). 

EUROASSAY: AMA Profile M2, M4, M9 

• Differentiation of mitochondrial antibodies (AMA). 


• Serum dilution 1 : 100; conjugate class anti-human IgGM, AP-labelled. 

• 3 relevant mitochondrial antibodies can be detected simultaneously and monospecifically: 

antibodies against M2, M4, M9. 

• Native antigens: pyruvate dehydrogenase complex (M2), sulfite oxidase (M4), 

gly cogen phosphorylase (M9). 

Anti- Associated diseases 

Rat kidney and M2 BIOCHIP: antibodies against 

mitochondria (AMA). 

M2 Primary biliary cirrhosis (high titers), other chronic liver diseases 

M4 Primary biliary cirrhosis 

M9 Early phase of primary biliary cirrhosis Incubated EUROASSAY AMA Profile M2, M4, M9. 

Microplate ELISA: Anti-M2-3E 

• Differentiation of mitochondrial antibodies (AMA). 



• Antibodies against M2 can be determined quantitatively in RU/ml. 

• Antigen: native pyruvate dehydrogenase complex plus recombinant M2 fusion 

protein (BPO) containing the immunogenic domains of the E2 subunits of PDH, 

BCOADH and OGDH. 


FA 1620-####-3 page 129 


DA 1620-####-1 O page 80 

Incubated ELISA anti-M2-3E. 


EA 1622-9601 G page 90 

— 39 — 





AG 



HEp-2 cells: anti-nuclear dots. Primate liver: 

anti-LSP. Rat kidney: AMA. Rat liver: ANA. Rat 

stomach: ASMA. VSM47.: Anti-F-actin. 


FA 1300-####-8 page 124 

Rat liver and rat kidney: antibodies against liverkidney 

microsomes (anti-LKM). 


FA 1300-####-1 page 124 

— 40 — 

Autoantibodies against Liver Antigens 

Indirect Immunofluorescence Test: Liver Mosaic 8 

• Screening and differentiation test for the detection of liver-specific antibodies, 

antibodies against mitochondria (AMA), antibodies against cell nuclei (ANA), 

antibodies against smooth muscles (ASMA), F-actin and other autoantibodies. 

• Indications: autoimmune hepatitis, primary biliary cirrhosis, rheumatic diseases. 


• The BIOCHIP Mosaic consists of 6 substrates: human epithelial cells (HEp-2), 

primate liver, rat kidney, rat liver, rat stomach, VSM47.. Thus, a broad spectrum 

of antigens is present, allowing not only targeted serological diagnoses, but also 

frequently yielding additional results with cli nical relevance. 

• Antibodies against cell nuclei (ANA) can be particularly well demonstrated using 

HEp-2 cells and primate liver, and are identified according to their fluorescence 

patterns. However, they also stain the cell nuclei of the other tissues more or 

less intensely. Clinical significance: rheumatic diseases, primary biliary cirr hosis 

(antibodies against nuclear dots). 

• With primate liver, several liver-specific autoantibodies can be investigated e.g. 

anti bodies against liver cell membrane (anti-LMA) and liver-specific protein 

(anti-LSP). Clinical significance: autoimmune hepa titis. 

• Antibodies against mitochondria (AMA) show a granular cytoplasmic fluorescence 

on all 6 substrates. With the standard substrate rat kidney, the proximal 

and distal tubule cells fluoresce equally. Clinical significance: primary biliary 

cirrhosis. 

• Autoantibodies against liver-kidney microsomes (anti-LKM) react with rat liver 

and rat kidney (see below). The other substrates are essentially negative. 

• In the case of autoantibodies against smooth muscles (ASMA), the tunica 

muscularis, the lamina muscularis mucosa as well as the interglandular contractile 

fibrils fluoresce on the rat stomach. ASMA directed against the target 

antigen F-actin furthermore react with the cytoskeleton of HEp-2 cells and the 

bile canaliculi of primate liver. The substrate VSM47. reacts very specifically, 

showing a filamentous, needle-like fluorescence. Clinical signifi cance: 

• 

autoimmune (lupoid) chronic active hepatitis. 

The BIOCHIP Mosaic can be supplemented as required with additional substrates, 

e.g. Crithidia luciliae (antibodies against dsDNA), musculus iliopsoas 

(antibodies against skeletal muscles), heart (anti bodies against striated muscles, 

antibodies against intercalated disks, AMA M7.), different EUROPLUS substrates 

(AMA-M2-3E, Sp100, gp210, PML, SLA/LP, LC-1, LKM). 

Indirect Immunofluorescence Test: BIOCHIP Mosaic Rat Liver/ 

Rat Kidney (Liver Mosaic 1) 

• Specific detection of antibodies against liver-kidney microsomes (anti-LKM). 

• Indications: autoimmune hepatitis, often associated with extrahepatic syndromes 

such as arthralgias, glomerulonephritis, vitiligo and chronic inflammatory bowel 

diseases. 


• Autoantibodies against liver-kidney microsomes react with rat liver and generate 

a smooth staining in the cytoplasm of the hepatocytes. 

• In rat kidney, particularly in the cortex area, a fine granular fluorescence of 

the proximal tubules – recognizable by the luminal brush border – is visible. 

The distal tubules are negative. The fluorescence intensity of the liver cells is 

normally stronger than that of the proximal renal tubules. 

• The differentiation between autoimmune hepatitis and virus-induced hepatitis 

can additionally be accomplished by investigating the appropriate viral 

parameters.



AG 

EUROLINE: Profile Autoimmune Liver Diseases 

• Differentiation of antibodies in autoimmune liver diseases. 

• Indications: autoimmune hepatitis, primary biliary cirrhosis, overlap syndromes. 


• With the EUROLINE Profile Autoimmune Liver Diseases, nine autoantibodies can 

be determined: anti bodies against AMA M2, M2-3E (BPO), Sp100, PML, gp210, 

LKM-1, LC-1, SLA/LP and Ro-52. 



• Further antigen combinations on page 82. 

Anti- Associated Diseases 

M2, Sp100, PML, gp210 Primary biliary cirrhosis 

LKM-1, SLA/LP, LC-1 Autoimmune hepatitis 

Ro-52 Autoimmune hepatitis, rheumatic diseases 

EUROASSAY: Liver Profile 

(Anti-M2, -LKM-1, LC-1, -SLA/LP) 

Autoantibodies against Liver Antigens 

• Determination of mitochondrial antibodies AMA M2, antibodies against liverkidney 

microsomes type 1 (LKM-1), antibodies against liver cytosolic antigen 

type 1 (LC-1), as well as of antibodies against soluble liver antigen/liver-pancreas 

antigen (SLA/LP). 

• Indication: autoimmune liver diseases. 


• Antibodies against M2, LKM-1, LC-1 and SLA/LP can be detected simultaneously 

and mono specifically. 

• Antigens: pyruvate dehydrogenase complex (M2, native), cytochrome P450 IID6 

(LKM-1, recombinant), formiminotransferase-cyclodeaminase (LC-1, recombinant) 

and soluble liver antigen/liver-pancreas antigen (SLA/LP, recombinant). 

Microplate ELISA: Anti-SLA/LP, Anti-LC-1, Anti-LKM-1 

3E (BPO) 

Sp100 

PML 

gp210 

LKM-1 

LC-1 

SLA/LP 

Ro-52 

Incubated EUROLINE Profile Autoimmune Liver 

Diseases. 

Incubated EUROASSAY M2, LKM-1, LC-1, SLA/LP. 

• Monospecific determination of antibodies against soluble liver antigen/liverpancreas 

antigen (SLA/LP), cytosolic liver antigen type 1 (LC-1) and liver-kidney 

microsomes type 1 (LKM-1). 

• Indication: autoimmune hepatitis. 


• 3-point calibration, quantitative (exception: Anti-LC-1, semi-quantitative). 

• Identical incubation conditions and times: all tests can be combined without 

difficulty on one and the same microplate. 

• Recombinant antigens: soluble liver antigen/liver-pancreas antigen (SLA/LP), 

formiminotransferase-cyclodeaminase (LC-1) and cytochrome P450 IID6 (LKM- 

1). The corresponding human cDNA was expressed in E. coli (SLA/LP) or insect 

cells (LC-1, LKM-1). Incubated ELISA Anti-SLA/LP, Anti-LC-1, Anti-LKM-1. 

AMA M2 

control 


DL 1300-1601-4 G page 82 


DA 1300-1003-3 G page 80 

Order No. (Anti-SLA/LP) Formats 

EA 1302-9601 G page 88 

— 41 — 





AG 



— 42 — 

Autoantibodies against Thyroid gland Antigens / Antigen Detections 

Thyroid gland, unfixed and thyroglobulin 

BIOCHIP: anti bodies against thyroid microsomes 

and thyro globulin. 


FA 1010-####-3 page 119 

RIA for thyroid diagnostics. 

Order No. (Anti-TPO) Formats 

RA 1012-####-# page 91 

Incubated ELISA Anti-Thyroid antigens. 

Order No. (Anti-TPO) Formats 

EA 1012-9601 G page 88 

Indirect Immunofluorescence Test: EUROPLUS Thyroid Gland 

(unfixed) and Thyroglobulin 

• Detection of antibodies against thyroid gland antigens. 

• Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis. 


• Using unfixed thyroid tissue, two important thyroid-specific antibodies can 

be found: Autoantibodies against thyroid microsomes (MAb) give a granular 

staining in the cytoplasm of the follicle epithelium (target antigen: thyroid 

peroxidase, TPO). Autoantibodies against thyroglobulin (TAb) react with the 

colloid of all follicles of the thyroid tissue and cause a reticular fluorescence 

pattern. 

• With the thyroglobulin-coated BIOCHIP, autoantibodies against thyroglobulin 

(TG) can be confirmed monospecifically in one and the same test procedure. 

• This BIOCHIP Mosaic can be supplemented as required with further substrates, 

e.g. rat kidney, to achieve a differentiation of antibodies against thyroid microsomes 

from mitochondrial antibodies (AMA). For a serological diagnosis of autoimmune 

polyendocrinopathies, BIOCHIPs with frozen sections of pancreas, 

adrenal gland, ovary, testis and stomach can be added. 

Radioimmunoassays (RIA/IRMA): Thyroid Specific Autoantibodies, 

Antigens and Hormones 

• Monospecific detection of autoantibodies against thyroglobulin (TG), thyroid 

peroxidase (TPO) and thyrotropin receptor (TSH-R). 

• Specific detection of the thyroid antigen thyrotropin and the hormones free 

triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), calcitonin. 

• Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis, medullary 

thyroid carcinoma, thyroidal C-cell hyperplasia, therapy controls in hyper- and 

hypothyrosis. 

• Serum dilutions: 1:50 for anti-TG and anti-TPO (magnetic), 1:20 for anti-TG and 

anti-TPO (precipitation), undiluted for all remaining test kits. 

• 5-point to 8-point calibration (quantitative). 

Analyte Order No. Analyte Order No. 

Anti-TPO RA 1012-####-# FT3 RD 1016-10001 

Anti-TG RA 1013-10001-# FT4 RD 1017.-10001 

TRAb RA 1015-10001-# TSH RD 1018-10001 

Thyroglobulin RD 1013-10001 Calcitonin RD 1019-10001 

Microplate ELISA: Anti-Thyroglobulin, Anti-Thyroid Peroxidase, 

Anti-TSH receptor 

• Monospecific determination of antibodies against thyroglobulin (TG), thyroid 

peroxidase (TPO), and thyrotropin receptor (TSH-R). 

• Indications: Basedow’s disease, Hashimoto autoimmune thyroiditis. 

• Serum dilution 1 : 200 (exception: anti-TSH-R undiluted); conjugate class antihuman 

IgG, POD-labelled (anti-TSH-R: avidin-labelled). 

• 3-point calibration (exception: anti-TSH-R, 5-point calibration). 

• The quantification is carried out according to international reference preparations 

(anti-TG: NIBSC 65/93; anti-TPO: NIBSC 66/387.; anti-TSH-R: NIBSC 90/67.2). 

• Thyroglobulin/TSH-R: native antigen; thyroid peroxidase: recombinant antigen. 


Thyroid peroxidase EA 1012-9601 G 

Thyroglobulin EA 1013-9601 G 

TSH receptor EA 1015-9601 G 

TSH receptor (Fast-ELISA) EA 1015-9601-1 G



AG 

Indirect Immunofluorescence test: Dermatology Mosaic 7. 

• Screening and differentiation test for detection of skin-specific antibodies. 

• Indication: bullous autoimmune dermatoses. 

Autoantibodies against Antigens of the Skin 


• The BIOCHIP Mosaic consists of 6 substrates: primate oesophagus, salt-split skin, 

desmoglein-1-expressing cells, desmoglein-3-expressing cells, BP230-expressing 

cells (gc) and BP180 (EUROPLUS). Thus a comprehensive antigen spectrum is 

available in a single analysis, allowing targeted serological diagnosis. 

• Antibodies against prickle cell desmosomes react with surface antigens of 

keratinocytes. Tissue sections of oesophagus and tongue show a granular 

fluo rescence of the intercellular matter in the whole stratum spinosum, but 

differentiation between desmoglein 1 and desmoglein 3 is difficult. When 

specific transfected cells are employed in addition, a targeted diagnosis in a 

single test run is possible. 

• Antibodies against basal membrane structures react with salt-split skin. Anti- 

BP180, anti-BP230 and anti–LAD97 cause staining of the epidermal side, and 

antibodies against laminin 5, collagen VII and other antigens staining of the 

dermal side of salt-split skin. 

• When autoantibodies against BP180 or BP230 are present, the epidermal basal 

membrane in the oesophagus or tongue is visible as a fine linear colouring 

between the stratum basale and the connective tissue. These antibodies can 

be differentiated by means of BP180-NC16A-4X coated BIOCHIPs and cells 

specifically transfected with BP230 (globular C-terminal domain (gC)). 

• This BIOCHIP Mosaic can be customised with further substrates if required, 

e.g. tongue (antibodies against prickle cell desmosomes, epidermal basal 

membrane), bladder (antibodies against plakins). 

Substrate Order No. 

Oesophagus FA 1501-#### 

Oesophagus / Tongue FA 1501-####-1 

Tongue FA 1502-#### 

Bladder mucosa FA 1507.-#### 

Salt split skin FA 150b-#### 

BP180-NC16A-4X / BP230gC FA 1502-####-1 

Envoplakin FA 1491-####-50 

Collagen type VII NC1 FA 1947.-####-50 

Microplate ELISA: Anti-Desmoglein 1, Anti-Desmoglein 3, Anti- 

Envoplakin, Anti-BP180-NC16A-4X, Anti-BP230-CF 

• Monospecific detection of antibodies against desmoglein 1, desmoglein 3, envoplakin, 

BP180 und BP230. 

• Indication: bullous autoimmune dermatoses. 


• 3-point calibration, quantitative (exception: anti-envoplakin, semiquantitative). 

• Identical incubation conditions and times: all tests can be combined on one 

microplate. 

• Recombinant antigens: extracellular domain of desmoglein 1 or 3, envoplakin, 

tetramer of NC16A domain of BP180 protein, C-terminal segment of BP230 

protein. The corresponding human cDNA is produced in E. coli (BP180-NC16A- 

4X, BP230-CF, envoplakin) or in mammalian cells (desmoglein 1, desmoglein 

3). 

Oesophagus and salt-split skin (top left, middle 

left): ab against epid. basal membrane. BP230 

gc (top right). BP180 (NC16A-4X) (middle right). 

Desmoglein 1 + 3 (bottom left and right). 


FA 1501-####-7. page 126 

Incubated ELISA Anti-Desmoglein 1 and 3, Anti- 

BP180-NC16A-4X, Anti-BP230-CF. 

Order No. (Anti-Dsg-1) Formats 

EA 1495-4801 G page 88 

— 43 — 





AG 



Cerebellum: antibodies against GAD and Yo (top), 

against Hu and Ri (middle). Peripheral nerves: 

anti bodies against myelin and MAG (bottom). 


FA 1111-####-1 page 120 

— 44 — 

amphiphysin 

CV2 

PNMA2 (Ma2/Ta) 

Ri 

Yo 

Hu 

control 

Incubated EUROLINE Neuronal Antigens Profile 2. 


DL 1111-1601-2 G page 82 

Autoantibodies against Neuronal Antigens 

Indirect Immunofluorescence Test: Neurology Mosaic 1 

• Screening test for the detection of antibodies against neuronal antigens. 

• Indications: neurological diseases. 

• Initial dilution 1 : 10; conjugate class anti-human IgAGM, FITC-labelled. 

• Primate cerebellum and primate nerves are the standard substrates for the 

determination of various neuronal antibodies. The parallel use of primate 

intestine permits the reliable differentiation from other autoantibodies (e.g. 

ANA) and makes it possible to distinguish between anti-Ri and anti-Hu. 

• Antibodies against grey matter react intensively with the stratum granulosum 

and in a weaker form with the stratum moleculare of the cerebellum. Target 

antigen: glutamic acid decarboxylase (GAD). Clinical significance: stiff person 

syndrome, dia betes mellitus type I. 

• Antibodies against Yo stain exclusively the cytoplasm of the Purkinje cells in the 

cerebellum. Clinical significance: paraneoplastic neurological syndromes (PNS), 

indi cation of a malignoma. 

• In the case of antibodies against Hu and Ri all neurone nuclei in the grey matter 

show a granular fluorescence. Hu antibodies react in the intestine with cell nuclei 

of the plexus myentericus, whereas Ri antibodies do not. Clinical significance: 

paraneoplastic neurological syndromes (PNS), indication of a malignoma. 

• The white matter of the cerebellum is stained by antibodies against myelin, 

which present as hyaline cylinders in tissue sections of peripheral nerves. A 

“droplike“ ring-shaped fluorescence is observed in cross sections of nerves. 

• The fluorescence of the Virchow-Robin space (cerebellum, optic nerve) and the 

pia is caused by autoantibodies developed in neuromyelitis optica (NMO-IgG). 

• Antibodies against myelin-associated glycoprotein (MAG), on the other hand, 

show a streaky fluorescence pattern on nerve tissue and a mostly fine-granular 

ring-shaped fluorescence on cross sections of peripheral nerves. Clinical 

significance: paraproteinaemic neuropathy. 

• The BIOCHIP Mosaic can be supplemented as required with further substrates, 

e.g. cerebrum (antibodies against astrocytes), optic nerve, primate liver plus 

HEp-2 cells (to rule out ANA), Crithidia luciliae (anti-dsDNA), primate stomach 

(parietal cell antibodies), Borrelia (neuroborreliosis-associated). Aquaporin- 

4(AQP4) transfected HEK cells allow a monospecific antibody determination in 

suspected cases of neuromyelitis optica (NMO). 

EUROLINE: Neuronal Antigens Profile 2 

• Differentiation of antibodies against neuronal antigens. 

• Indication: paraneoplastic neurologic syndromes (PNS). 


• With the EUROLINE Neuronal Antigens Profile 2, six autoantibodies can be 

determined: anti bodies against amphiphysin, CV2, PNMA2 (Ma2/Ta), Ri, Yo and 

Hu. 


EUROBlotMaster und EUROLineScan (see page 27.).



AG 

EUROLINE-WB: Anti-Neuronal Antigens 

Autoantibodies against Neuronal Antigens 

Indirect Immunofluorescence Test: Autoimmune Encephalitis 

Mosaic 1 

• Screening test for detection of neuropil antibodies (glutamate receptors type 

NMDA and type AMPA, LGI1, CASPR2, GABA receptors). 

B 

• Indication: autoimmune encephalitis. 


• Immunohistochemistry with tissue sections of rat hippocampus and rat 

• 

cerebellum allows identification of antibodies against glutamate receptors (type 

NMDA, type AMPA) and other antibodies (e.g. VGKC-associated proteins LGI1 

and CASPR2). The parallel use of transfected HEK293 cells enables sensitive 

and monospecific antibody detection and differentiation of various neuropil 

antibodies. 

Neuropil antibodies show a flat, smooth to fine-granular fluorescence in the 

cytoplasm of transfected HEK293 cells. Clinical significance: autoimmune 

encephalitis. 

• Determination of human autoantibodies against neuronal antigens. 

• Indication: paraneoplastic neurological syndromes (PNS). 



of a primate cerebellum extract are electrophoretically separated according to 

molecular mass and transferred onto a nitrocellulose membrane (westernblot). 

A membrane chip coated with highly purified recombinant Hu, recombinant Ri 

and recombinant Yo is subsequently applied to the westernblot strip. 

• Test strips can be automatically incubated using the system EUROBlotMaster 

(Seite 27.). 

Transfected cells: antibodies against NMDAR 

and CASPR2 (top), AMPAR1 and LGI1 (middle), 

AMPAR2 and GABA B -R (bottom). 


FA 112d-####-1 page 121 

Yo Ri 

Ri 

Yo 

rec. Yo 


DW 1111-####-2 G page 86 

Hu 

rec. Ri 

rec. Hu 

Control 

Incubated Anti-Neuronal Antigens EUROLINE-WB. 

— 45 — 





AG 



Primate pancreas: antibodies against islet cells. 


FA 1020-#### page 119 

Incubated ELISA anti-GAD. 

Order No. (Anti-GAD) Formats 

EA 1022-9601 G page 88 

RIA Anti-IA2. 

Order No. (Anti-IA2) Formats 

RA 1023-#### page 91 

— 46 — 

Autoantibodies against Islet Cell Antigens 

Indirect Immunofluorescence Test: Primate Pancreas 

• Detection of antibodies against islet cells. 

• Indications: Differentiation between a late manifestation of diabetes type 1 

(latent autoimmune diabetes in adulthood, LADA) and diabetes type 2. 

• For a reliable determination of antibodies against islet cells an extended 

incubation time of 18 hours for the patient serum must be observed. The 

incubation time may be reduced to 2 hours but this will lead to a decrease in 

the sensitivity of the antibody detection test. 

• Standardised control with JDF units available (order no. CA 1021-0101-1). 

• With indirect immunofluorescence autoantibodies against pancreas islets 

• 

(ICA) can be detected in 80% of patients with new-onset diabetes type 1. Two 

target antigens of ICA have been identified so far: the enzymes glutamic acid 

decarboxylase (GAD) and tyrosine phosphatase (IA2). 

This BIOCHIP may be supplemented with further substrates, e. g. primate 

cerebellum for the detection of antibodies against GAD. 

• The microscopic evaluation can be significantly simplified by using small 

BIOCHIPs (1 x 1 mm). The BIOCHIPs appear almost completely in the field 

of view and facilitate finding the islet cells, thus rendering a time-consuming 

search unnecessary, especially in negative samples. 

Microplate ELISA: Anti-GAD, Anti-IA2, Anti-GAD/IA2 Pool 

• Monospecific detection of antibodies against glutamic acid decarboxylase (GAD), 

tyrosine phosphatase (IA2) or bispecific detection of both antibodies in a single 

reagent well. 

• Indications: early diagnosis of diabetes mellitus type 1, risk prediction in 

first grade relatives, prognosis of the clinical progression of diabetes type 1 

for prediction of insulin dependence, differential diagnosis in gestational 

diabetes, differentiation between a late manifestation of diabetes type 1 (latent 

autoimmune diabetes in adulthood, LADA) and diabetes type 2. 

• Use of undiluted samples. Similar incubation conditions and times. Manual or 

automated test performance. 

• Multipoint calibration. The quantitation is based on an international reference 

preparation (NIBSC 97./550). 

• GAD and IA2: human, recombinant antigens. 

Antigen Order no. 

Glutamic acid decarboxylase (GAD) EA 1022-9601 G 

Tyrosine phosphatase (IA2) EA 1023-9601 G 

GAD/IA2 Pool EA 1022-9601-1 G 

RIA: Anti-GAD, Anti-IA2, Anti-Insulin 

• Monospecific detection of antibodies against glutamic acid decarboxylase (GAD), 

tyrosine phosphatase (IA2) and insulin. 

• Indications: Early diagnosis of diabetes mellitus type 1, risk prediction in 

first grade relatives, prognosis of the clinical progression of diabetes type 1 

for prediction of insulin dependence, differen tial diagnosis in gestational 

diabetes, differentiation between a late manifestation of diabetes type 1 (laten t 

autoimmune diabetes in adulthood, LADA) and diabetes type 2. 

• Use of undiluted samples. Similar incubation conditions and times. Manual or 

automated test performance. 

• Test kit formats for 50 or 100 determinations. 

• GAD and IA2: human, recombinant, 125 I-labelled antigens, insulin: human, 

synthetic, 125 I-labelled antigen. 

Antigen Order no. 

Glutamat-Decarboxylase (GAD) RA 1022-#### 

Tyrosin-Phosphatase (IA2) RA 1023-#### 

Insulin RA 1024-####



AG 

Indirect Immunfluorescence Test: Primate Stomach with Urea 

Pretreatment 

• Screening test for detection of antibodies against parietal cells. 

• Indications: forms of chronic atrophic gastritis, pernicious anemia, funicular 

myelosis, various autoimmune endocrinopathies such as Basedow’s and 

Addison’s diseases. 

• Initial dilution 1 : 10; polyvalent conjugate anti-human IgG, FITC-labelled. 

• Primate stomach is the standard substrate for detection of parietal cell antibodies. 

For titration, stomach tissue from rat or mouse is sufficient. 

• With positive results the parietal cells show a course granular to clumpy 

fluorescence, and the surrounding areas are usually dark. 

• Parietal cell antibodies (PCA) are often mixed up with antibodies against 

mitochondria (AMA) in microscopic analysis. The latter give an even fine 

granular fluorescence of the parietal cell cytoplasm, with the surrounding region 

showing a (weaker) reaction. 

• For reliable differentiation of both types of antibody, a 30-minute pretreatment 

of the tissue sections with urea-glycine buffer (order no. ZF 1140-0101, see page 

143) is recommended. 

• The cytomplasmic fluorescence of parietal cells resulting from PCA occurs with 

the same intensity with or without urea pretreatment. The typical pattern of 

mitochondrial antibodies is almost completely supressed by urea pretreatment, 

greatly facilitating PCA diagnostics. 

• In some AMA-positive samples it is possible to detect PCA that are obscured by 

the AMA pattern in conventional tissue sections. 

• The urea-pretreated tissue shows a significantly darker background, enabling 

specific fluorescence to be more easily and reliable identified. 

• This BIOCHIP can be supplemented with additional substrates, for example, 

thyroid (thyroid peroxidase, thyroglobulin), pancreas (pancreas islets), adrenal 

gland (adrenal cortex), ovary (ovary antigens), testis (Leydig cells), and intrinsic 

factor. 

Microplate ELISA: Anti-Parietal Cells 

Autoantibodies against Parietal Cells (PCA) 

• Monospecific detection of antibodies against parietal cells (PCA). 

• Indications: forms of chronic atrophic gastritis, pernicious anemia, funicular 

myelosis, various autoimmune endocrinopathies such as Basedow’s and 

Addison’s diseases 



• Native antigen: H + /K + -ATPase, purified by affinity chromatography. 

Primate stomach: antibodies against parietal 

cells. With urea-pretreatment (top) and without 

urea-pretreatment (bottom). 

Primate stomach: antibodies against mitochondria. 

With urea-pretreatment (top) and without 

urea-pretreatment (bottom). 


FA 1360-#### page 124 

Incubated ELISA Anti-Parietal Cells. 


EA 1361-9601 G page 88 

— 47. — 





AG 



— 48 — 

Autoantibodies against granulocyte Cytoplasm (cANCA/pANCA) 

EUROPLUS Granulocyte Mosaic 25 (granuloc. 

(EOH), granuloc. (HCHO), PR3, MPO, GBM, HEp-2 

+ granuloc. (EOH)): pANCA. 


FA 1201-####-25 page 123 

Incubated ELISA ANCA Profile (antigens: proteinase 

3, lactoferrin, myeloperoxidase, elastase, 

cathepsin G, BPI. 


EA 1200-1208-1 G page 88 

Indirect Immunofluorescence Test: EUROPLUS Granulocyte 

Mosaic 25 

• Screening test for the detection of antibodies against granulocyte cytoplasm 

(ANCA). 

• Indications: Wegener‘s granulomatosis, various forms of glomerulonephritis, 

primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease. 

• Initial dilution: serum 1 : 10; conjugate anti-human IgG, FITC-labelled. 

• Using ethanol-fixed granulocytes, antibodies against granulocyte cytoplasm can 

be detected. In this case, two fluorescence patterns have to be differentiated: 

a granular fluorescence which is distributed evenly over the entire cytoplasm, 

leaving the cell nuclei free (cyto plasmic type, cANCA) or a smooth fluorescence 

wrapped ribbon-like around the cell nuclei (perinuclear type, pANCA). 

• Antibodies against all relevant granulocyte antigens as well as against further, 

as yet unknown antigens are detected simultaneously: 

Pattern Target antigen Associated diseases 

cANCA Proteinase 3 Wegener‘s granulomatosis 

pANCA Myeloperoxidase Microscopic arteritis, Churg-Strauss syndrome, 

polyarteritis nodosa 

pANCA Elastase Ulcerative colitis, Crohn’s disease, primary sclerosing 

cholangitis, systemic lupus erythema tosus 

pANCA Cathepsin G Ulcerative colitis, primary sclerosing cholangitis, 

Crohn’s disease 

pANCA Lysozyme Ulcerative colitis, primary sclerosing cholangitis, 

Crohn’s disease 

pANCA Lactoferrin Ulcerative colitis, primary sclerosing cholangitis, 

Crohn’s disease, systemic lupus erythema tosus, 

rheumatoid arthritis 

cANCA BPI Primary sclerosing cholangitis, ulcerative colitis, 

or pANCA Crohn’s disease 

pANCA unknown Ulcerative colitis, Crohn’s disease 

• The composite substrate HEp-2 cells + granulocytes enables one to differentiate 

between pANCA and anti-nuclear antibodies (ANA) which can easily be confused 

when using ethanol-fixed granu lo cytes: In the case of a positive ANA result all 

nuclei of the HEp-2 cells fluoresce, whereas in the case of pANCA (as well as 

cANCA) only the granulocytes fluoresce. 

• The EUROPLUS substrates PR3 and MPO as monospecific tests can confirm 

results from conventional granulocyte screening tests. Recombinant GBM 

EUROPLUS substrate also provides additional reliability for diagnosis. When 

fluorescence patterns are unclear (e.g. unspecific fluorescence caused by other 

cytoplasmic antibodies) these substrates facilitate evaluation. 

Microplate ELISA: ANCA Profile 

• Differentiation of antibodies against granulocyte cytoplasm (ANCA). 

• Indications: Wegener‘s granulomatosis, various forms of glomerulonephritis, 

primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease. 


• 6 relevant anti-granulocyte antibodies can be detected simultaneously and 

monospecifically: autoantibodies against pro teinase 3, lactoferrin, myeloperoxidase, 

elastase, cathepsin G, BPI. 

• 1-point calibration, semi-quantitative. Calibrator pool and serum sample on the 

same microplate strip. 

• Native antigens, purified by affinity chromatography. 

• Available individual ELISA (3-point calibration, quantitative): 


Proteinase 3 (PR3-hn-hr: native/recombinant) EA 1201-9601-2 G 

Myeloperoxidase EA 1211-9601 G



AG 

Autoantibodies against CIBDRelevant Antigens 

Indirect Immunofluorescence test: CIBD Profile 

• Screening and differentiation test for the detection of antibodies in chronic 

inflammatory bowel diseases (CIBD): pancreas antigens rPAg1 and rPAg2, 

intestinal goblet cells, granulocytes (EOH), lactoferrin-specific (LFS) granulocytes, 

Saccharomyces cerevisiae. 

• Indication: Crohn‘s disease, ulcerative colitis. 

• Initial dilution: pancreas antigens, intestinal goblet cells and granulocytes 1:10 

(IgA, IgG), S. cerevisiae 1:100 (IgA), 1:1000 (IgG). 

• For serological diagnosis of ulcerative colitis the indirect immunofluorescence 

test uses goblet cells (differentiated intestinal cells) for the detection of 

autoantibodies against intestinal goblet cells, and ethanol-fixed (EOH-fixed) 

granulocytes for the detection of anti-neutrophil cytoplasmic antibodies 

(ANCA). Another important antibody associated with ulcerative colitis is directed 

against DNA-bound lactoferrin. For the determination of these autoantibodies 

granulocytes selectively reacting with lactoferrin (LFS granulocytes) are used. 

• The investigation of antibodies against against exocrine pancreas (rPAg 1 + 2) 

and antibodies against S. cerevisiae is used for serological diagnosis of Crohn‘s 

disease. For the detection of antibodies against pancreas antigens rPAg1 

(CUZD1) and rPAg2 (gP2) transfected cells are used as the standard substrate. 

• Differential diagnosis is most efficient using a substrate combination of goblet 

cells, granulocytes, rPAg1 / rPAg2 and S. cerevisiae. If LFS granulocytes are 

used in addition (e.g. FA 1391-####-4), the hit rate for the serological diagnosis 

of chronic inflammatory bowel diseases can be increased significantly. 

Transfected cells: autoantibodies against CUZD1 

and GP2 (top); EOH-fixed and LFS granulocytes 

(middle); intestinal goblet cells and S. cerevisiae 

(bottom). 


FA 1391-####-4 page 125 

— 49 — 




M edizinische 



EUROIMMUN AG 

AG 



Cost-Effective Strategy for the Detection of 

Autoantibodies against Granulocyte Cytoplasm (ANCA) 

Screening test using indirect immunofluorescence BIOCHIP sextet: granulocytes (EOH), granulocytes 

(HCHO), EUROPLUS microdots PR3, MPO and GBM, and human epithelial cells (HEp-2) plus granulocytes 

A 

Granulocytes 

(EOH-fixed) 

B 

Granulocytes 

(HCHO-fixed) 

C 

EUROPLUS 

PR3 

microdots 

At B cytoplasmic 

fluorescence 

pANCA & GBM & MPO 

ELISA: Anti-MPO/Anti-GBM 

AAb against 

MPO 

Goodpasture Syn. 30-60 % 

F 

HEp-2 cells 

+ 

granulocytes 

(EOH-fixed) 

E 

EUROPLUS 

GBM 

microdots 

D 

EUROPLUS 

MPO 

microdots 

MPA 53 % 

AAb against 

GBM 

Perinuclear fluorescence of 

granulocytes (A, F) 

MPA 42-70 % 

CSS 18-60 % 

SLE 9-25 % 

RA 3-25 % 

pANCA 

At B no cytoplasmic 

fluorescence 

DNA-ANCA 

UC 67 % 

CD 7 % 

PSC 87 % 

ELISA: ANCA Profile 

AAb against PR3, MPO, 

elastase, cathepsin G, 

BPI, lactoferrin 

WG 5 % (BPI) 

MPA 53 % (MPO) 

MPA 3 % (LF) 

RA, vasculitides 45 % (LF) 

SLE 6 % (EL) 

Fluorescence of all cell nuclei 

(A, F) 

only ANA 

Cytoplasmic fluorescence 

of granulocytes (B) 

pANCA & ANA & MPO 

MPA 42-70 % 

Qualified ANA diagnostics: screening test using 

HEp-2 cells + granulocytes (F), differentiation 

using ELISA, EUROASSAY, EUROLINE, Westernblot 

AAb against dsDNA, ssDNA, nucleosomes, 

histones, nuclear membrane, nRNP/Sm, Sm, 

SS-A, Ro-52, SS-B, Ku, cyclin I (PCNA), mitosin 

(CENP-F, cyclin II), nuclear dots, centromeres 

(CENP B), spindle fibres, midbody, centrioles, 

Scl-70, PM-Scl, fibrillarin, RNA polymerase I, 

NOR, ribosomal P-proteins, Jo-1, PL-7, PL-12, 

Mi-2, mitochondria (AMA), lysosomes, Golgi 

apparatus, vimentin, tropomyosin, actin. 

Fluorescence of all cell nuclei 

(A, F), granuloc. accentuated (F) 

ANA and pANCA 

Nuclei of granuloc. brighter than 

nuclei of HEp-2 cells (F), B neg. 

DNA-ANCA & ANA 

cANCA 

WG 80-90 % 

MPA 10-15 % 

CSS 10-20 % 

PAN < 9 % 

ELISA: Anti-PR3-hn-hr / ANCA Profile (BPI) 

AAb against 

PR3-hn-hr 

WG 80-90 % 

Cytoplasmic fluorescence 

of granulocytes (A, B, F) 

ANCA reaction at A, 

ANA reaction at F 

DNA-ANCA? & ANA 

AAb against 

BPI 

WG 5 % 

See EUROIMMUN poster: " Strategy for Determination 

of Autoantibodies against Cell Nuclei (ANA) 

and Cytoplasm Components" 

The highest diagnostic sensitivity in the determination of autoantibodies against neutrophil granulocytes (ANCA) is achieved by using indirect immunofluorescence 

and assays with defined target antigens (particularly PR3, MPO and GBM) simultaneously at the start. However, under the pressure of cost optimisation, an immunofluorescence 

test may be performed on its own and then followed up by specific ELISA tests only if the result is positive. Ethanol-fixed human granulocytes 

are the standard substrate for indirect immunofluorescence. With this substrate two relevant fluorescence patterns can be differentiated: the cytoplasmic type 

(cANCA) associated with Wegener’s granulomatosis and the perinuclear type (pANCA), which indicates a range of various diseases. The differentiation of pANCA 

from antibodies against cell nuclei (ANA) is often difficult. Therefore, HEp-2 cells (possibly with sedimented granulocytes) or primate liver are used as an additional 

substrate. If ANA and pANCA occur together, the granulocytes show a much brighter fluorescence than the cell nuclei. Thanks to EUROIMMUN BIOCHIPs it is not 

necessary to incubate human epithelial cells on a second slide in parallel for the exclusion of cell nucleus antibodies, since all substrates are present in one and the 

same test field. A third BIOCHIP with formalin-fixed human granulocytes detects a large proportion of the diagnostically relevant antibodies against myeloperoxidase, 

whereas other pANCA (which are particularly important in gastroenterology) and almost all antibodies against cell nuclei (whose differentiation is a separate 

chapter in autoantibody diagnostics) are generally completely suppressed. The EUROPLUS substrates PR3, MPO, GBM help to confirm diagnosis and allow a quick 

and reliable interpretation of results even in problematic cases. 

ANA: anti-nuclear antibodies BPI: bactericidal permeability increasing protein cANCA: anti-neutrophil cytoplasmic antibodies, cytoplasmic type CD: Crohn‘s disease CSS: Churg-Strauss syndrome EL: elastase EOH: ethanol 

HCHO: formalin HEp-2: human epithelial cells IFT: immunofluorescence test LF: lactoferrin MPA: microscopic polyangiitis MPO: myeloperoxidase PAN: polyarteritis nodosa pANCA: anti-neutrophil cytoplasmic antibodies, 

perinuclear type PR3: proteinase 3 PSC: primary sclerosing cholangitis RA: rheumatoid arthritis SLE: systemic lupus erythematosus UC: ulcerative colitis WG: Wegener‘s granulomatosis 

EUROIMMUN — 50 — AG · D-23560 Luebeck (Germany) · Seekamp 31 · Phone +49 451 58550 · Fax 5855591 · E-mail euroimmun@euroimmun.de 

HA_1200_I_UK_A04, 09/2011



AG 

Autoantibodies against Phospholipase A 2 Receptor (PLA 2 R) 

Indirect Immunofluorescence test: Anti-Phospholipase A 2 Receptor 

• Detection of antibodies against phospholipase A 2 receptor (PLA 2 R). 

• Indication: primary membranous glomerulonephritis (MGN, also idiopathic 

membranous nephropathy IMN). 

• Initial dilution 1 : 10; conjugate class anti-human IgG, FITC labelled. 

• The Anti-Phospholipase A 2 receptor IIFT uses transfected cells as the standard 

substrate. Antibodies against PLA 2 R react with the transfected cells of the test 

substrate. They induce a cytoplasmic fluorescence, with some fluorescence of 

the cell membrane. 

Infl uence of rituximab therapy on autoantibodies against 

phospholipase A2 receptor (PLA2R) in patients with 

membranous glomerulonephritis (MN) 

recombinant protein 

Schematic illustration of PLA2R isoform 1 

Introduction 

Idiopathic membranous glomerulonephritis 

(IMN) is the leading cause of nephrotic 

syndrome in Caucasian adults. One third 

of the patients have a progressive loss of 

renal function up to end-stage renal failure. 

PLA2R-specifi c antibodies might be involved 

in disease induction and their detection and 

quantifi cation may become an important 

tool to guide and monitor therapy. 

Methods 

Autoantibodies against PLA2R were determined 

in serum from 12 patients with 

biopsy-proven MN by indirect immunofl uorescence 

(IF). Formalin-fi xed HEK293 cells, 

which were transiently transfected with fulllength 

PLA2R isoform 1 cDNA, were used 

as IF substrates. In addition to supportive 

therapy (ACE-i, ARB, diuretics, statins, 

anti-coagulation) or immunosuppressive 

therapy (3 patients with glucocorticoids, 2 

with glucocorticoids + MMF, 1 with glucocorticoids 

+ CNI), all patients were treated 

with 375 mg/m² rituximab (RTX). 10 patients 

had at least 1 immunosuppressive therapy 

before RTX therapy. 

E. Hoxha 1 , K. Fechner 2 , S. Harendza 1 , R.A.K. Stahl 1 

¹ Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany 

² Institute of Experimental Immunology, affi liated to EUROIMMUN AG, Luebeck, Germany 

cysteine-rich domain 

fibronectin type II domain 

c-type lectin-like domains 

transmembrane domain 

intracellular tail 

HEK293 cells transfected with 

recombinant full-length PLA2R isoform 1 

Results 

7 of 12 patients showed autoantibodies 

against PLA2R. Following RTX immunosuppressive 

therapy, there were decreasing 

anti-PLA2R antibody levels in 5 cases: 3 

patients within 1 week, 1 patient within 1 

month, 1 patient within 3 months, 1 patient 

had constant levels over 3 months. 1 patient 

showed an increasing titer after 3 months. 

The latter 2 patients never showed decreasing 

anti-PLA2R antibody levels after RTX. In 

2 other patients anti-PLA2R antibody levels 

decreased after RTX therapy and increased 

again after 3 months and 12 months, respectively. 

3 patients had no detectable 

autoantibody levels after 3 and 6 months. 

Proteinuria decreased in all patients with 

a decrease in antibody titers. Patients with 

an increase in antibody titers had a parallel 

increase in proteinuria. 

Conclusion 

Patients with biopsy-proven MN had anti- 

PLA2R autoantibodies in 58.3% of cases. 

Changes in antibody titer upon RTX therapy 

were paralleled by changes in proteinuria. 

Non-transfected HEK293 cells 

These results indicate that anti-PLA2R 

antibodies may help to guide and monitor 

therapeutic decisions in patients with IMN 

following RTX. However, these findings 

should be proven in a prospective study 

using a larger cohort. 

Proteinuria [mg/24 h] 

Anti-PLA2R titer 

350 

300 

250 

200 

150 

100 

50 

0 

16000 

14000 

12000 

10000 

8000 

6000 

4000 

2000 

0 


FA 1254-####-50 page 123 

1 2 3 4 5 6 7 8 9 10 11 12 

1 2 3 4 5 6 7 8 9 10 11 12 

Time of measurement 

1: 1st RTX 

2: 1 week after 1st RTX 

3: 4 weeks after 1st RTX 

4: 3 months after 1st RTX 

5: 6 months after 1st RTX 

6: 2nd RTX 

7: 1 week after 2nd RTX 

8: 4 weeks after 2nd RTX 

9: 3 months after 2nd RTX 




Anti-PLA 2 R titer (IFT using PLA 2 R transfected cells) and 

changes in proteinuria in patient 3 following rituximab 

(RTX) therapy. 

Scientifi c presentation at the 11 th International Workshop on Autoantibodies and Autoimmunity (IWAA), Shanghai, China, May 2011 

— 51 — 





AG 



Primate liver and gliadin (GAF-3X) BIOCHIP: antibodies 

against endomysium and gliadin. 


FA 1914-####-1 A or G page 131 

Incubated ELISA Anti-Gliadin (GAF-3X). 


EV 3011-9601 A or G page 98 

Incubated ELISA Anti-Tissue Trans glutaminase 

(Endomysium). 


EA 1910-9601 A or G page 90 

— 52 — 

Antibodies against Endomysium and gliadin 

Indirect Immunofluorescence Test: EUROPLUS Primate Liver 

and Gliadin (GAF-3X) BIOCHIPs 

• Detection of antibodies against endomysium and gliadin. 

• Indications: gluten-sensitive enteropathy (celiac disease, non-tropical sprue), 

Duhring’s herpetiform derma titis. 

• Initial dilution 1 : 10; conjugate class anti-human IgA or IgG, primate absorbed, 

FITC-labelled. 

• Autoantibodies against endomysium react with many types of tissue, e.g. 

primate oesophagus. The most suitable substrate, however, is primate liver: in 

the case of a positive sample, filamentous linings of the intralobular sinusoids 

react. 

• With the gliadin (GAF-3X)-coated BIOCHIP, antibodies against gliadin can be 

analyzed in one and the same test procedure. 

• Both anti-endomysium antibodies and antibodies against gliadin (class IgA) are 

reliable serological markers for an active gluten-sensitive entero pathy. Therefore, 

their determination can in many cases replace endoscopy and biopsy. 

Microplate ELISA: Anti-Gliadin (GAF-3X) 

• Monospecific detection of antibodies against gliadin. 



• Serum dilution 1 : 200; conjugate class anti-human IgA or IgG, POD-labelled. 

• 3-point calibration. Identical incubation conditions and times: the investigation 

of IgA and IgG antibodies can be combined without difficulty on one and the 

same microplate. 

• Antigen: Gliadin-analogue fusion peptide (GAF-3X). 

• The quantitative determination of antibodies against gliadin is very suitable for 

monitoring the progress of the disease, compliance with a gluten-free diet, or a 

gluten tolerance test. 

Microplate ELISA: Anti-Tissue Transglutaminase (Endomysium) 

• Monospecific detection of antibodies against tissue transglutaminase. 



• Serum dilution 1 : 200; conjugate class anti-human IgA or IgG, POD-labelled. 


• Antigen: recombinant, expression with the baculovirus vector in insect cells.



AG 

EUROIMMUN PRODUCTS FOR INFECTIOUS SEROLOgY 

— 53 — 

EUROIMMUN Products for 

Infectious Serology



AG 


Infectious Serology 

Antibodies against Borrelia afzelii, VlsE (top), 

Borrelia burgdorferi and OspC (bottom). 


FI 2136-####-1 G or M page 133 

Incubated ELISA Anti-Borrelia plus VlsE. 


EI 2132-9601 G or M page 93 

Table-based evaluation of the CSQ rel. 


EI 2132-9601-L G or M page 93 

— 54 — 

Antibodies against Borrelia 

Indirect Immunofluorescence Test: EUROPLUS Anti-Borrelia 

afzelii, Borrelia burgdorferi, VlsE and OspC Antigen 

• Sensitive screening test for the detection of anti-Borrelia antibodies. 

• Indications: erythema chronicum migrans, lymphadenosis cutis benigna, lymphocytic 

meningoradiculitis, carditis, arthritis, acrodermatitis chronica atrophicans, 

neuroborreliosis. 

• Initial dilution 1 : 10 (IgM), 1 : 100 (IgG). 

• If antibodies against Borrelia afzelii or Borrelia burgdorferi are present, a distinct 

fluorescence of the bacteria in the smear is obtained. 

• With the VlsE or OspC coated BIOCHIPs antibodies against the highly specific 

and highly sensitive marker antigens VlsE (IgG) or OspC (IgM) can be determined 

monospecifically in one and the same test procedure. If these antigens fluoresce 

the antibody result is positive even if the bacteria smears show a negative 

reaction. Thus, the BIOCHIP Mosaic helps to increase specificity and sensitivity 

in Borrelia diagnostics. 

• The BIOCHIP can be supplemented as required using further substrates, e.g. 

Borrelia burgdorferi sensu stricto (strains CH or USA) and TBE virus infected 

cells. 

Microplate ELISA: Anti-Borrelia plus VlsE 

• Sensitive screening test for the detection of anti-Borrelia antibodies. 




• Serum dilution 1:101; conjugate class anti-IgG or anti-IgM (VlsE: -IgG only), PODlabelled. 

• 3-point calibration (IgG and IgM). Identical incubation conditions and times: all 

tests can be combined without difficulty on one and the same microplate. 

• Antigens: extract of Borrelia burgdorferi sensu stricto, Borrelia garinii and 

Borrelia afzelii (whole antigen) / recombinant VlsE from Borrelia burgdorferi 

sensu stricto (IgG). VlsE (variable major protein-like sequence, expressed) is 

a surface protein of Borrelia which is expressed exclusively in vivo and which 

contains conserved and highly immunogenic epitopes. 

• IgM test kit (Anti-Borrelia) includes IgG/RF absorbent in sample buffer for IgG 

absorption in preparation for the determination of specific IgM class antibodies. 

Microplate ELISA: Anti-Borrelia plus VlsE, Antibody Determination 

in Serum and Cerebrospinal Fluid for Detection of Intrathecal 

Synthesis of Specific Antibodies against Borrelia 

• Antibody determination in serum and cerebrospinal fluid (CSF). 

• Indication: Neuroborreliosis. 

• CSF dilution 1 : 2, serum dilution 1 : 404; conjugate class anti-IgG or anti-IgM, 

POD-labelled. 

• 4-point calibration, quantitative.



AG 

Anti-Borrelia EUROLINE-RN-AT 

Antibodies against Borrelia 

• Specific confirmatory test for the detection of antibodies against Borrelia. 




• The Anti-Borrelia EUROLINE provides a unique mixture of Borrelia specific 

antigens in a user-friendly line blot format. In addition to the major serological 

early markers OspC (IgM) and VlsE (IgG) – in each case from B. afzelii, B. 

burgdorferi and B. garinii – it contains highly specific p39 (Bmp) and the late 

marker p38. Five new, recombinant designer antigens (p18, p19, p20, p21, p58) 

having a very high specificity (IgG) were identified using bioinformatic analysis 

of the Borrelia genome. For the first time, lipids which have been proven to be 

immunoreactive and were extracted from the Borrelia membrane are available 

on the line blot. 

• The Anti-Borrelia EUROLINE-RN-AT (IgG) can also be used for qualitative detection 

of specific intrathecal antibody synthesis in neuroborreliosis. 

• The serological hit rate is increased by 10% by using three OspC variants in the 

IgM test. 

• Serum dilution 1 : 51; conjugate class anti-IgG or anti-IgM, AP-labelled. 

EUROLINE-WB: Anti-Borrelia (Whole Antigen plus VlsE) 

• Specific confirmatory test for the detection of antibodies against Borrelia. 

• EUROLINE-WB is a combination of westernblot and line blot techniques. An SDS 

extract of a Borrelia afzelii strain is electrophoretically separated according to 

molecular mass and transferred onto a nitrocellulose membrane. A membrane 

chip coated with highly purified recombinant VlsE-Antigen is then added to the 

westernblot strips. 

• By additionally determining antibodies against VlsE the serological hit rate 

can be increased by 20% compared to whole extract Western blots and by 30% 

compared to recombinant antigen Westernblots. Of all recombi nant antigens, 

VlsE possesses the highest sensitivity for the detection of a Borrelia infection. 

Over 85% of IgG-positive sera could be identified at a glance by assessing the 

VlsE band. VlsE allows detection of antibodies against all Borrelia species, and the 

risk of a false negative reaction due to species differences is ten times lower. 


VlsE B. burgd. 

p41 

p39 

OspC B. afzelii 

OspC B. burgd. 

OspC B. garinii 

IgM 

Control band 

Automated Evaluation of Incubated Membrane Strips with the System EUROLineScan 

VlsE B. afzelii 

VlsE B. burgdorferi 

VlsE B. garinii 

Lipid B. afzelii 

Lipid B. burgdorferi 

p83 

p41 

p39 

VlsE 

p 83 

p 41, Flag. 

p 39, Bmp A 

p 31, Osp A 

p 30 

p 25, Osp C 

• The program EUROLineScan from EUROIMMUN has been developed to enable quantitative evaluation of membrane based test systems, 

facilitate management of data, and provide detailed documentation of results — tasks which have until now required con siderable time. 

• First, the incubated test strips are scanned using a flatbed scanner or camera system. 

• EUROLineScan recognizes the position of the strips, even if they have been placed inexactly, identifies the bands, and measures their 

inten sity. The auto mated evalu ation can be moni tored, and it is possible to supplement the data manually. 

• The results are then saved together with the image data. It is no longer necessary to archive (potentially infectious) incubated test strips. 

A separate results sheet can be produced for each patient. 

p 21 

p 19 

p 17. 

OspC 

p58 

p21 

p20 

p19 

p18 

Igg 

Incubated Anti-Borrelia EUROLINE-RN-AT . 


DN 2131-3201 G or M page 83 

Control band 

Control band 

Incubated EUROLINE-WB Anti-Borrelia. 


DY 2131-1601-1 G or M page 86 

— 55 — 


Infectious Serology



AG 



— 56 — 

Antibodies against EpsteinBarr virus (EBv) 

Patient 1: EBV-CA (IgG) EBV-CA (IgG): urea-treated EBV-CA (IgM) EBV-EA (IgG) EBNA (IgG) 

Patient 2: EBV-CA (IgG) EBV-CA (IgG): urea-treated EBV-CA (IgM) EBV-EA (IgG) EBNA (IgG) 

Indirect Immunofluorescence Test: BIOCHIP Sequence EBV 

• Gold standard for the determination of antibodies against the EBV-CA antigens (Epstein-Barr virus capsid antigen), EBV-EA (Epstein- 

Barr early antigen) and EBNA (Epstein-Barr nuclear antigen). 

• Indication: infectious mononucleosis, Burkitt‘s lymphoma, nasopharyngeal carcinoma (NPC). 

• IgG antibodies against EBV-CA indicate an EBV infection. An at least twofold increase in titer and the absence of antibodies against 

EBNA at the same time is characteristic for the early phase of the infection. IgM antibodies against EBV-CA and antibodies against 

EBV-EA can also be found in acute infections, but they do not necessarily always occur. The presence of antibodies against EBNA 

generally indicates the late phase of an EBNA infection. 

• In cases of an acute EBV infection which cannot be reliably discriminated from a relapse or reinfection, the determination of the 

antibody avidity using a modified immunofluorescence test as an additional parameter is useful. This requires an additional incubation 

with urea solution (ZF 1130-0801). The determination of low-avidity antibodies against EBV-CA indicates an acute infection. 

• For the monospecific confirmation of EBV-CA antibodies in the same test procedure the BIOCHIP containing ECV-CA is supplemented 

with the antigen substrates gp125 antigen (native) and p19 antigen (recombinant) (EUROPLUS FI 27.91-####-20 G or M). 

• For highly differentiated diagnostics the BIOCHIP Sequence EBV (FI 2799-####-1 X) can be supplemented by using the antigens gp125 

and p19 (EUROPLUS FI 2799-####-21 X). 

• Due to the high prevalence of anti-EBV-CA IgA in NPC patients, the parameter is well suited for screening. Confirmation of the result 

by determination of IgA antibodies against EBV-EA is recommended. Further anti-EBV test kits for indirect immunofluorescence: 

Substrate Order No. Substrate Order No. 


FI 2799-####-21 X page 141 

Incubated ELISA Anti-EBNA-1. 

Order No. (anti-EBNA-1) Formats 

EI 27.93-9601 G page 97. 

EBV-CA FI 27.91-#### A, G or M EBV-EA FI 27.95-#### A or G 

EBNA FI 27.93-#### G EBV-CA & EBV-EA FI 27.91-####-2 A or G 

Microplate ELISA: Anti-EBV-CA, Anti-EBNA-1, Anti-EBV-EA 

• Specific confirmatory test for antibodies against EBV-CA, EBNA-1 or EBV-EA. 

• Indications: infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal 

carcinoma. 

• Serum dilution 1 : 101; conjugate class anti-IgA, -IgG or IgM, POD-labelled. 

• 1-point calibration, semi-quantitative (IgA, IgM) or 3-point calibration, quantitative 

(IgG). Identical incubation conditions and times: all tests can be combined 

without difficulty on one and the same microplate. 

• EBV-CA: native antigen, purified by affinity chromatography; EBNA-1 and EBV-EA: 

recom binant antigen. 

• IgM test kit includes IgG/RF absorbent in sample buffer for IgG absorption in 

preparation for the determination of specific IgM class antibodies. 

• Available individual ELISA: 


EBV-CA EI 27.91-9601 A, G or M 

EBNA-1 EI 27.93-9601 G 

EBV-EA EI 27.95-9601 A, G or M 

fresh infection 

previous infection



AG 

Antibodies against EpsteinBarr virus (EBv) 

Determination of Low-Avidity Antibodies against EBV-CA 

• An alternative principle for the serological diagnosis of fresh infections with EBV 

has been established by investigating the antibody avidity. 





• To identify low-avidity antibodies against EBV-CA in a patient’s serum, two 

micro plate ELISA or immunofluorescence tests are performed in parallel: one 

test is carried out in the conventional way, the other one includes urea treatment 

between incubations with patient’s serum and per oxidase-labelled anti-human 

IgG, resulting in the detachment of low-avidity antibodies from the antigens. 

• Low-avidity antibodies against EBV-CA are present if the ELISA extinction is 

significantly reduced by urea treatment. For an objective interpretation, the 

relative avidity index (RAI) can be calculated out of the measured values with 

and without urea incubation. 

• With the immunofluorescence test the presence of low-avidity antibodies has 

been proved if the test using urea treatment gives a far weaker fluorescence 

than the two-step test. 

EUROLINE: EBV Profile 2 

• Differentiation of antibodies against Epstein-Barr virus antigens. 


carcinoma. 

• Serum dilution 1 : 100; conjugate class anti-human IgG or IgM, AP-labelled. 

• With the EUROLINE EBV Profile 2, five different antibodies can be determined: 

anti bodies against VCA gp125, VCA p19, EBNA-1, p22, EA-D. 

• Recombinant antigens (exception: VCA gp125, native, purified by affinity chromatography). 

• EBNA-1 (IgG) negative und VCA (IgG and IgM) positive: acute (fresh) infection. 

• EBNA-1 (IgG) and VCA (IgG) positive and VCA (IgM) negative: late phase of 

infection. 

• EBNA-1 (IgG) negative, but band p22 (IgG) and VCA (IgG) positive: late phase of 

infection with loss of anti-EBNA-1. 



Westernblot: Anti-EBV 

• Specific confirmatory test for the detection of antibodies against Epstein-Barr 

virus antigens, differentiation of antibodies against Epstein-Barr virus antigens. 


carcinoma. 


• Antigens: whole antigen, SDS extract. 

• Bands from all specific antigens are included and clearly separated. 

• EBNA-1 (IgG) negative und VCA (IgG and IgM) positive: acute (fresh) infection. 

• EBNA-1 (IgG) and VCA (IgG) positive and VCA (IgM) negative: late phase of 

infection. 

• EBNA-1 (IgG) negative, but band p22 (IgG) and VCA (IgG) positive: late phase of 

infection with loss of anti-EBNA-1. 



Number of Patients 

10 

8 

6 

4 

2 

0 

0 25 50 75 100 

VCA gp125 

VCA p19 

EBNA-1 

p22 

EA-D 


DN 27.90-1601-2 G or M page 83 

VCA 125 

VCA 65 

VCA 40/41/42 

Relative Avidity Index (RAI) in % 

Avidity of antibodies against EBV-CA (IgG). 

VCA 33 

VCA 22 

RAI = E with urea 

E without urea 

Incubated Westernblot Anti-EBV. 


DY 27.90-1501 G or M page 87. 

Primary Infection 

Previous Infection 

Order No. (IIFT) 

FI 2791-#### X 

Order No. (ELISA) Formats 

EI 27.91-####-1 G page 97. and 140 

Control IgG/IgM 

Incubated EUROLINE EBV Profile 2. 

EA R 

EBNA-1 

EA D 

Control band 

— 57. — 


Infectious Serology



AG 



Antibodies against Helicobacter pylori. 


FI 2080-#### A, G or M page 133 

Incubated ELISA Anti-Helicobacter pylori. 


EI 2080-9601 A or G page 93 

— 58 — 

Antibodies against helicobacter pylori 

p 120, CagA 

p 95, VacA 

p 66, UreB 

p 33 

p 30 

p 29, UreA 

p 26 

p 19, OMP 

p 17. 

Alignment bar 

Control band 

Incubated EUROLINE-WB Anti-Helicobacter pylori. 


DY 2080-1601-1 A or G page 86 

Indirect Immunofluorescence Test: Anti-Helico bacter pylori 

• Sensitive screening test for the detection of antibodies against Helicobacter 

pylori. 

• Indications: gastritis, ulcus ventriculi et duodeni. Late consequences: MALT 

lympho mas and adenocarcinomas. 

• Initial dilution 1 : 10 (IgM), 1 : 100 (IgG), 1 : 32 (IgA). 

• If antibodies against Helicobacter pylori are present, a distinct fluorescence of 

the bacteria in the smear is obtained. 

• A positive IgA result correlates well with the activity of a gastritis. An increased 

IgG antibody titer is considered to be a marker for chronic infections. A significant 

drop in the IgG antibody titer about 6 months after therapy is a sign of 

success. 

• The BIOCHIP can be supplemented as required with further substrates, e.g. other 

infectious agents or tissue sections of primate stomach. 

Microplate ELISA: Anti-Helicobacter pylori 

• Sensitive screening test for the detection of antibodies against Helicobacter 

pylori. 



• Serum dilution 1 : 101; conjugate class anti-IgA or anti-IgG, POD-labelled. 

• Antibodies against Helicobacter pylori antigens can be determined quantitatively 

in RU/ml. 

• 1-point calibration, semi-quantitative (IgA) or 3-point calibration, quantitative 

(IgG). Identical incubation conditions and times: both tests can be combined 


• Native antigens. 

EUROLINE-WB: Anti-Helicobacter pylori 

• Specific confirmatory test for the detection of antibodies against Helicobacter 

pylori. 



• Serum dilution 1 : 50; conjugate class anti-IgA or anti-IgG, AP-labelled. 

• EUROLINE-WB is a combination of westernblot and line blot techniques. An 

SDS extract of a Helicobacter pylori strain is electrophoretically separated 

according to molecular mass and transferred onto a nitrocellulose membrane 

(westernblot). Two membrane chips coated with highly purified recombinant 

CagA and VacA are subsequently applied to the westernblot strips. 



EUROBlotMaster und EUROLineScan (see page 27.).



AG 

Antibodies against herpes Simplex virus (hSv) 

Indirect Immunofluorescence Test: BIOCHIP Mosaic HSV-1/HSV-2 

• Sensitive screening test for the detection of antibodies against herpes simplex 

viruses. 

• Indication: herpes simplex. 

• Initial dilution 1 : 10 (IgM), 1 : 100 (IgG). 

• If antibodies against herpes simplex-2 virus are present in the sample, a typical 

fluorescence of the infected cells is obtained – mainly in the outspread cytoplasm, 

less in the cell nuclei. 

• As HSV-1 and HSV-2 are morphologically and immunologically closely related, 

cross-reactions can occur. Differentiation may be attempted by testing a serum 

against both antigen substrates and comparing the titers. 

• The BIOCHIP Mosaic can be supplemented as required with further substrates, 

e.g. other infectious agents. 

• Anti-HSV individual tests for indirect immunofluorescence: 

Substrate Order No. 

HSV-1 FI 2531-#### G or M 

HSV-2 FI 2532-#### G or M 

HSV-1 and -2 FI 2531-####-1 G or M 

Microplate ELISA: Anti-HSV-1, Anti-HSV-2 

• Specific confirmatory tests for antibodies against HSV-1 or HSV-2. 


• Serum dilution 1 : 101; conjugate class anti-IgG or anti-IgM, POD-labelled. 

• 1-point calibration, semiquantitative (IgM) or 3-point calibration, quantitative 

(IgG). Identical incubation conditions and times: all tests can be combined 


• Antigens: type-specific glycoproteins C1 or G2, purified by affinity chromatography. 

Cross-reactions do not occur. 



• Available individual ELISA: 


HSV-1 EI 2531-9601-2 G or M 

HSV-2 EI 2532-9601-2 G or M 

HSV-1/2-Pool EI 2531-9601-1 G or M 

EUROLINE-WB: Anti-HSV 

• Specific confirmatory test for the differentiation of antibodies against HSV-1 and 

HSV-2. 




from an SDS extract of HSV-1 are electrophoretically separated according to 

molecular mass and transferred onto a nitrocellulose membrane. A membrane 

chip coated with HSV-2 type-specific glycoprotein G2 (gG 2), purified by affinity 

chromatography, is then added to the westernblot strips. 


• The gG 2 band allows the simple differentiation between HSV-1 and HSV-2 

infections. 



Antibodies against HSV-1 and HSV-2. 


FI 2531-####-1 G or M page 147. 

Incubated ELISA Anti-HSV-1. 

Order No. (anti-HSV-1) Formats 

EI 2531-9601-2 G or M page 95 

gC 1 

gG 1 

gG 2 

Alignment bar 

Control band 

Incubated EUROLINE-WB Anti-HSV. 


DY 2531-1601-1 G or M page 87. 

— 59 — 


Infectious Serology



AG 



Anti-Chlamydia MIF. 


FI 2191-####-3 A, G or M page 135 

Incubated ELISA Anti-Chlamydia trachomatis. 


EI 2191-9601 A, G or M page 94 

Incubated ELISA Anti-Chlamydia pneumoniae. 


EI 2192-9601 A, G or M page 94 

— 60 — 

Antibodies against Chlamydia 

Indirect Immunofluorescence test: Anti-Chlamydia MIF (Micro- 

Immunofluorescence test) 

• Serological gold standard for the determination of antibodies against Chlamydia. 

• Indication: trachoma, urogenital infections, lymphogranuloma venereum, laryngitis, 

sinusitis, bronchitis, pneumonia, psittacosis. 

• Initial dilution 1 : 10 (IgA), 1 : 100 (IgG), 1 : 10 (IgM). 

• The micro-immunofluorescence test uses purified elementary bodies of the 

species C. trachomatis, C. pneumoniae and C. psittaci as the antigen. The mutual 

lipopolysaccharide (LPS) antigen is inactivated to minimise cross reactivity. 

• The evaluation of the MIF could be significantly facilitated compared to conventional 

test systems by using a cell-based substrate. 

• The fourth BIOCHIP with non-infected cells allows a reliable differentiation 

between unspecific and specific fluorescence. 

Microplate ELISA: Anti-Chlamydia trachomatis 

• Monospecific detection of antibodies against Chlamydia trachomatis. 

• Indication: trachoma, conjunctivitis, urogenital infections, pneumonia in infants, 

lymphogranuloma venereum. 

• Serum dilution 1:101, conjugate class anti-human IgA, IgG or IgM, POD-labelled. 

• 1-point calibration, semiquantitative (IgA and IgM) or 3-point calibration, quantitative 

(IgG). 

• Antigen: native MOMP antigen (major outer membrane protein). MOMP is a 

transmembrane protein and represents the main part of the outer membrane of 

the elementary bodies. Protein purification starts with BGM cells infected with 

Chlamydia trachomatis of the serotype K. 



Microplate ELISA: Anti-Chlamydia pneumoniae 

• Monospecific detection of antibodies against Chlamydia pneumoniae. 

• Indication: laryngitis, sinusitis, bronchitis, pneumonia. 

• Serum dilution 1: 101, conjugate class anti-human IgA, IgG or IgM, POD-labelled. 

• 1-point calibration, semiquantitative (IgA and IgM) or 3-point calibration, quantitative 

(IgG). 

• Antigen: cell lysate from HL cells, strain CDC/CWL-029. 


preparation for the determination of specific IgM class antibodies.



AG 

Indirect Immunofluorescence Test 

Antibodies against Emerging viruses 

• Over the past years it has been observed that a number of new viruses ( „ emerging“ 

or „ reemerging viruses“) and other pathogens has spread worldwide, introducing 

since then unknown diseases into previously unaffected regions. 

• EUROIMMUN offers a broad spectrum of indirect immunofluorescence tests for 

the detection of specific antibodies against: 

Pathogen Disease, syndromes see page 

Corona virus SARS corona virus (SARS-CoV) 

Flaviviruses 

Bunyaviruses 

Togaviruses 

• Many of these substrates are available as single substrate with non-infected 

cells or as useful combinations (syndrome or geographically orientated) for the 

in vestigation of serum samples. 

• IgG absorption as preparatory step for the determination of specific antibodies 

of class IgM: page 64. 

• Cross reactions within the virus family, especially with Flaviviruses, should be 

taken into consideration since they may cause false-positive results. The infectious 

agent can be determined by titration of the sample and comparison of 

titers. 

Microplate ELISA: Anti-TBE Virus, Anti-West Nile Virus, 

Anti-Dengue Virus 

• Monospecific determination of antibodies against TBE, West Nile and Dengue 

virus. 

• Serum dilution 1: 101, conjugate class anti-human IgG or IgM, POD-labelled. 

• 1-point calibration, semiquantitative (IgM) or 3-point calibration, quantitative 

(IgG). Similar incubation conditions and times: All tests can be combined on one 

and the same microplate. 

• IgM test kit with IgG/RF absorbent in the sample buffer for IgG absorption as 

preparatory step for the determination of specific IgM antibodies. 

• Available single ELISA: 


Severe acute respiratory syndrome 

(SARS) 

TBE virus (TBEV) Tick-borne encephalitis 138 

West Nile virus (WNV) West Nile fever, encephalitis 138 

Japanese encephalitis virus (JEV) Japanese encephalitis 138, 141 

Yellow fever virus (YFV) 

Yellow fever, hepatitis, haemorrhagic 

fever, arthritis 

Dengue virus (DENV, types 1-4) Dengue fever, haemorrhagic fever 138, 141 

Hantavirus (types HTNV, PUUV, 

SEOV, SAAV, DOBV, SNV, ANDV) 

Sandfly fever virus (types SFSV, 

SFNV, TOSV, CYPV) 

Rift valley fever virus (RVFV) 

Crimean-Congo fever virus 

(CCHFV-GPC and -N) 

HFRS (haemorrhagic fever with renal 

syndrome); HCPS (Hantaviral cardiopulmonary 

syndrome) 

Pappataci fever, meningitis, 

encephalitis 

Rift valley fever, haemorrhagic fever, 

hepatitis 

TBE EI 2661-9601 G or M, avidity, Ab determination in CSF 

TBE „Vienna“ EI 2661-9601-9 G 

WNV EI 2662-9601 G or M, avidity 

Dengue EI 266b-9601 G or M 

137. 

138 

139 

139 

Crimean-Congo haemorrhagic fever 141 

139, 141 

Chikungunya virus (CHIKV) Chikungunya fever, arthritis 141, 142 

Sindbis virus (SINV) Sindbis fever 142 

Kinetoplastida Leishmania donovani Visceral leishmaniasis 136 

haemosporina 

Plasmodium falciparum Malaria tropica 136, 141 

Plasmodium vivax Malaria tertiana 136, 141 

SARS-CoV TBEV 

WNV 

JEV YFV DENV 

PUUV 

ANDV 

SFSV 

RVFV CCHFV CHIKV 

SINV 

Leish. donov. 

Plasmodium 

Incubated ELISA Anti-TBE virus, Anti-WNV, Anti- 

Dengue virus. 

Order No. (Anti-TBE) Formats 

EI 2661-9601 G or M page 96 

— 61 — 


Infectious Serology



AG 



FI 282110011 g FI 282210011 g 

RESPIRATORY TRACT PROFILE 1 EXANThEMA PROFILE 1 

Igg IgM Igg IgM 

Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10 

V Verification BIOCHIP*** V Verification BIOCHIP*** 

1. RSV 1. HHV-6 

2. Adenovirus type 3 2. Rubella virus* 

3. Influenza virus type A (H1N1) 3. Measles virus 

4. Influenza virus type A (H3N2) 4. Mumps virus 

Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10 

5. Influenza virus type B 5. VZV 

6. Parainfluenza virus type 1 6. EBV-CA** 

7.. Parainfluenza virus type 2 7.. EBV-EA 

8. Parainfluenza virus type 3 8. Treponema pallidum 

Field C 1 : 10 1 : 10 Field C 1 : 100 1 : 10 

9. Parainfluenza virus type 4 9. HSV-1 

10. Bordetella pertussis** 10. HSV-2 

11. Bordetella parapertussis** 11. Coxsackie virus type B1 

12. Mycoplasma pneumoniae 12. Coxsackie virus type A9 

Field D 1 : 100 1 : 10 Field D 1 : 100 1 : 10 

13. Coxsackie virus type B1 13. Echo virus type 7. 

14. Coxsackie virus type A7. 14. Borrelia afzelii 

15. Echo virus type 7. 15. Borrelia burgdorferi sensu stricto (CH) 

16. Chlamydia pneumoniae 16. Borrelia garinii 

Field E 1 : 100 1 : 100 Field E 1 : 100 1 : 100 

17.. Haemophilus influenzae* , ** 17.. CMV 

18. Klebsiella pneumoniae* 18. Candida albicans** 

19. Legionella pneumophila serotype 1* , ** 19. Candida krusei* , ** 

20. Legionella pneumophila serotype 12* , ** 20. Candida tropicalis* , ** 

FI 282310011 g FI 282410011 g 

LYMPhADENITIS PROFILE 1 CENTRAL NERvOUS SYSTEM PROFILE 1 


Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10 


1. HIV-1* 1. Rubella virus* 

2. HIV-2* 2. Measles virus 

3. HHV-6 3. Mumps virus 

4. Rubella virus* 4. VZV 

Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10 

5. Measles virus 5. Adenovirus type 3 

6. Mumps virus 6. EBV-CA** 

7.. Adenovirus type 3 7.. Treponema pallidum 

8. Parainfluenza virus type 1 8. Toxoplasma gondii** 

Field C 1 : 10 1 : 10 Field C 1 : 100 1 : 10 

9. EBV-CA** 9. HSV-1 

10. EBV-EA 10. HSV-2 

11. Toxoplasma gondii** 11. Coxsackie virus type B1 

12. Treponema pallidum 12. Coxsackie virus type A7. 

Field D 1 : 100 1 : 10 Field D 1 : 100 1 : 10 

13. HSV-1 13. Echo virus type 7. 

14. HSV-2 14. Borrelia afzelii 

15. CMV** 15. Borrelia burgdorferi sensu stricto (CH) 

16. Coxsackie virus type B5 16. Borrelia garinii 

Field E 1 : 100 1 : 10 Field E 1 : 100 1 : 100 

17.. Coxsackie virus type A9 17.. CMV 

18. Bartonella henselae** 18. Haemophilus influenzae* , ** 

19. Chlamydia trachomatis** 19. Listeria monocytogenes 1/2a 

20. Chlamydia pneumoniae 20. Listeria monocytogenes 4b 

— 62 — 

BIOChIP Mosaics for Infectious Serology 

(For formats see pages 141) 

* For clinical evaluation the results must be confirmed with a CE approved test. 

** For practical reasons the recommended incubation differs from the standard incubation for this substrate. 

*** Field A contains a verification BIOCHIP. The incubation was performed correctly if the dots show a visible colour reaction. 

BIOCHIP Mosaics containing fewer substrates can be produced upon request.



AG 

BIOChIP Mosaics for Infectious Serology 

(For formats see pages 141) 

FI 282510011 g FI 282610011 g 

MYOCARDITIS PROFILE 1 INFECTIOUS ARThRITIS PROFILE 1 


Field A 1 : 10 1 : 10 Field A 1 : 10 1 : 10 


1. Mumps virus 1. VZV 

2. Adenovirus type 3 2. Influenza virus type A (H1N1) 

3. Influenza virus type A (H1N1) 3. Influenza virus type A (H3N2) 

4. Influenza virus type A (H3N2) 4. Influenza virus type B 

Field B 1 : 10 1 : 10 Field B 1 : 10 1 : 10 

5. Influenza virus type B 5. Yersinia enterocolitica O:3* , ** 

6. Parainfluenza virus type 1 6. Yersinia enterocolitica O:6* , ** 

7.. Parainfluenza virus type 2 7.. Yersinia enterocolitica O:9* , ** 

8. Mycoplasma pneumoniae 8. Toxoplasma gondii** 

Field C 1 : 100 1 : 10 Field C 1 : 100 1 : 10 

9. CMV** 9. Borrelia afzelii 

10. Coxsackie virus type B1 10. Borrelia burgdorferi sensu stricto (CH) 

11. Coxsackie virus type A16 11. Borrelia garinii 

12. Echo virus type 7. 12. Chlamydia trachomatis** 

Field D 1 : 100 1 : 10 

13. Borrelia afzelii 

14. Borrelia burgdorferi sensu stricto (CH) 

15. Borrelia garinii 

16. Chlamydia pneumoniae 

RSV 

Adenovirus 

type 3 

Influenza 

virus type A 

(H3N2) 

Influenza 

virus type A 

(H1N1) 

Influenza 

virus type B 

Parainfluenza 

virus type 1 

Parainfluenza 

virus type 3 

Parainfluenza 

virus type 2 

Parainfluenza 

virus type 4 

Bordetella 

pertussis 

Mycoplasma 

pneumoniae 

Bordetella 

parapertussis 

* For clinical evaluation the results must be confirmed with a CE approved test. 

** For practical reasons the recommended incubation differs from the standard incubation for this substrate. 

*** Field A contains a verification BIOCHIP. The incubation was performed correctly if the dots show a visible colour reaction. 

BIOCHIP Mosaics containing fewer substrates can be produced upon request. 

Coxsackievirus 

type B1 

Coxsackievirus 

type A7 

Chlamydia 

pneumoniae 

Echovirus 

type 7 

Haemophilus 

influenzae 

Klebsiella 

pneumoniae 

Legionella 

pneumophila 

serotype 1 

Legionella 

pneumophila 

serotype 12 

— 63 — 


Infectious Serology



AG 



— 64 — 

absorbent 

Additional Reagents for the Determination of Acute Infections 

EUROSORB IgG/RF Absorbent. 


ZF 127.0-0145 page 144 

rheumatoid factor 

IgG 

Reagents for determination of low-avidity antibodies 

in infectious serology. 


ZF 1130 und ZF 1131 page 143 

IgG Absorpion 

• Before a patient’s serum is tested for specific antibodies of the IgM class, 

anti bodies of class IgG must be removed, for example by ultracentrifugation, 

chromato graphy or immunoabsorption. 

• Specifically bound IgG would displace IgM from the antigen leading to false IgM 

negative test results. 

• Moreover, the absorption prevents any IgM class rheumatoid factors present 

from reacting with specifically bound IgG and thus leading to false IgM positive 

test results. 

• Indication: an IgG absorption of serum samples should always be performed 

for all IgM antibody determinations in infectious serology before incubating the 

sera. 

• IgG/RF absorbent is contained in the sample buffer in all ELISAs for infectious 

serology (class IgM). 

EUROSORB IgG/RF Absorbent for Indirect Immunofluorescence 

• Functional principle: the EUROSORB reagent contains an anti-human IgG antibody 

preparation from goat. Immunoglobulin G of a serum or plasma sample is 

bound with high specificity by these antibodies and precipitated. If the sample 

also contains rheumatoid factors, these will be absorbed by the anti-human 

IgG/IgG complex. 

• Incubation time of the sample with the reagent is 15 minutes. 

• All IgG subclasses are bound and precipitated by the anti-human IgG antibodies. 

• Human serum IgG in concentrations of up to 15 mg/ml and rheumatoid factors 

are completely removed by the absorbent (average se rum IgG concentration in 

adults: 12 mg/ml). 

• The recovery rate of the IgM fraction is almost 100%. 

• One unit contains 4.5 ml absorbent, sufficient for the absorption of 100 serum 

samples. 

Urea Solutions and Avidity Buffers for the Determination of Low- 

Avidity Antibodies in Infectious Serology 

• To identify low-avidity antibodies in a patient’s serum, two immunofluorescence 

tests are performed in parallel: one test is carried out in the conventional way, 

the other one includes urea treatment between incubations with patient’s serum 



• Low-avidity antibodies are present if the fluorescence intensity is significantly 

reduced (two intensity levels ore more) by urea treatment. 

• The following reagents for avidity determination are available: 

IFT, Ab against Order No. Avidity Solution Incubation Time 

Rubella ZF 1130-0501 urea solution, 5 M 10 min 

WNV ZF 1130-0601 urea solution, 6 M 10 min 

Toxopl. ZF 1130-0801 urea solution, 8 M 10 min 

EBV-EA, EBV-CA ZF 1130-0801 urea solution, 8 M 30 min 

CMV ZF 1131-0101-1 avidity buffer 1 10 min 

VZV ZF 1131-0101-2 avidity buffer 2 30 min



AG 

EUROIMMUN PRODUCTS FOR ALLERgOLOgY 

— 65 — 


Allergology



AG 


Allergology 

Incubated EUROLINE Allergy Profile Inhalation. 

Incubated ELISA Total IgE. 

— 66 — 

Grasses 

Trees 

Weeds 

Mites 

Animal hair 

Mould spores 

CCD 

Indicator 


DP ####-1601 E Page 83 


EV 3840-9601 E Page 98 

Allercoat TM 6 ELISA. 


EP ####-0110 E Page 99-118 

ZP ####-#### E 

Antibodies of Class IgE against Allergens 

EUROLINE: Specific IgE 

• Determination of specific IgE in serum. 

• Indication: Clarification of allergic reactions to inhalation allergens, food 

allergens and cross-reactive allergens (pollen-associated food allergies). 

• Serum dilution: undiluted (or 1 : 10); conjugate class anti-IgE (monoclonal), APlabelled. 

• Antibodies against up to 36 allergens per strip can be simultaneously monospecifically 

detected. 

• EUROLINE profiles with different allergen compositions are available for various 

test requirements: atopy, inhalation, food, insect venoms and cross reactions. 

• The programme EUROLine Scan from EURO IMMUN has been developed to 

enable semi-quantitative evaluation of membrane-based test systems, facilitate 

management of data, and provide detailed documentation of results. 

• The incubated EUROLINE test strips are scanned using a flatbed scanner. 

EUROLine Scan recognises the position of the strips, identi fies the bands, and 

measures their inten sity. 

EUROIMMUN Microplate ELISA: Total IgE 

• Determination of the total IgE concentration in serum. 

• Indications: Differentiation between allergic and intrinsic asthma, between 

allergic and vasomotor rhinitis, and between atopic and seborrhoic dermatitis. 

• Serum dilution 1 : 10; conjugate class anti-IgE (monoclonal), POD-labelled. 

• One microplate well incubated per patient. 


• Coating: anti-human IgE, polyclonal. 

• The Total IgE ELISA serves as a screening test for allergy diagnostics and 

provides an indication for the presence of an allergic reaction. 

Allercoat 6 Microplate ELISA: Specific IgE 

• Determination of allergen-specific IgE concentrations in serum. 

• Indication: identification of allergic reactions to more than 600 different allergens 

and allergen mixtures. 

• Serum dilution: undiluted, conjugate class anti-human IgE, AP-labelled. 

• One microplate well per allergen/allergen mixture is incubated for each patient. 

• Calibration: 6-point calibration, quantitative; using reference preparation 2 IRP 

7.5/502 from the WHO. 

• The allergens are coupled to paper rings and can be flexibly configured for each 

sample according to the analysis. 

• Customized pre-assembled microplates with individual allergy parameters are 

available on request (Order no.: EP 9901-0101). Orders can be made online with 

the provided software. Please contact us! 

• A light table and special evaluation software are available to supplement the 

simple manual Allercoat 6 ELISA procedure. 

• Allercoat 6 ELISA are automatable using the EUROIMMUN Analyzer I and the 

EUROIMMUN Allercoat software.



AG 

Antibodies of Class IgE against Allergens 

Customized Laboratory Software for Flexible Automation of 

Allercoat System 

• Convenient online ordering of individual pre-prepared Allercoat microtiter 

plates. 

• Integrated light table for manual preparation of ELISA plates and sample 

distribution. 

• Direct control of photometer, automated evaluation via calibration curve and 

compilation of results. 

• Fully automated incubation of samples and evaluation of results via connection 

to the EUROIMMUN Analyzer I. 

• Fully automated administration, documentation and archiving of all data. 

• Simple operation using graphic user commands and clear presentation of the 

most important information at a glance. 

• Connection to commonly used laboratory systems for convenient transfer of 

requests and results. 

• Additional security through user administration with individual access rights 

and confirmation step before results editing. 

Individual equipment 

with allergen rings 


Incubate: 60 min, 37. °C 


per well 




per well 




Evaluate: photometric measurement 

at a wavelength of 405 nm 

allergen rings 

undiluted 

samples 

enzyme 

conjugate 

chromogen- 

/substrate sol. 

stop 

solution 

Allercoat TM Software. 

Fitting of allergen rings into 

microplate wells 

— 67. — 


Allergology



AG 

general Delivery Conditions 

Products from EUROIMMUN will be delivered according to the following conditions, as long as no other conditions have been agreed in 

writing. On issuing an order, the buyer acknowledges the delivery conditions. EUROIMMUN does not accept the sales conditions of the 

buyer, even when EUROIMMUN has not expressly contradicted them. Contract terms are valid for all future business connection even if 

they have not been expressly agreed upon again. 

Orders: Orders to EUROIMMUN can be made in writing (including electronic communication) or verbally. Verbally issued orders first 

become legally binding for EUROIMMUN with a written confirmation from the orderer or with the delivery of goods. 

Delivery: EUROIMMUN Medizinische Labordiagnosika AG (EUROIMMUN) generally delivers to end users within 7. days of order receipt and 

to distributors within 14 days, but is not tied to any definite delivery period. If a delivery is not possible through unforseeable circumstances 

(e.g., factory disruptions, raw material delivery delays, transport difficulties, strikes), the delivery obligation does not apply. EURO IMMUN 

reserves the right to deliver in part. The delivery obligation of EUROIMMUN ceases as long as the customer is in arrears. EUROIMMUN 

chooses the packing and dispatching method at its own discretion, according to the respective requirements. 

Product characteristics: The delivered products comply with specifications given in the product catalogue, on the product itself, or in 

the supplied information sheets. If specifications are inconsistent, the labels on the product itself and the details in the information sheet 

provided with the product apply. After the given expiration date has passed, the test reagents must not be used. 

EUROIMMUN products must only be used for the intended purpose. It is the buyer’s responsibility to check the functional capability 

immediately on receipt of the product as well as on every day of usage. In particular, the functioning of test reagents can be perturbed 

through causes outside the direct influence of the maunfacturer, for example, through suboptimal transportation, incorrect storage, 

or incorrect usage. When test reagents delivered from EUROIMMUN are used, the user must supervise the analysis with appropriate 

proficiency. 

Warranty and liability: If nothing else has been agreed upon in writing, all risks pass to the buyer as soon as the goods have been 

delivered to the carrier or has left EUROIMMUN premises for dispatch. With notification of dispatch by EUROIMMUN the risk passes to the 

buyer if the delivery is postponed or delayed by request of the buyer. On receipt of the goods, the buyer has one working day to check if 

they are in accordance with the nature and quantity of the agreement and if the goods are free from visible defects. If any complaints arise 

from this inspection, they should be communicated to EUROIMMUN in writing within 2 working days. Hidden defects or functional faults 

that were not identifiable with the initial inspection and are later discovered should be communicated to EUROIMMUN in writing within 

14 days of receipt of the goods. If no complaints are received within the stipulated period, it is assumed that the goods are of appropriate 

quality and quantity for the customer. Complaints do not release the buyer from payment obligation. 

With prompt and reasonable complaints on the grounds of product defects or the delivery of something other than the ordered goods, 

EUROIMMUN is obliged to exchange or amend the goods within 14 days or to withdraw or reimbourse the payment, as it chooses. If the 

defect is not corrected in spite of delivery of a replacement or an amended product, the buyer can demand that the sale is cancelled. 

If defects are promptly reclaimed, EUROIMMUN has the choice between a further delivery or an appropriate credit note. Further compensatory 

claims from the buyer are excluded, as long as EUROIMMUN has not violated its contractual or legal obligations through outright negligence 

or by intention. In such cases EUROIMMUN provides compensation of up to a maximum of 20 times the price of one packet (test kit) of 

the defective product. EUROIMMUN takes no responsibility for any damage resulting from faulty goods. 

Prices: Prices from the official EUROIMMUN pricelist in the country of the buyer are applicable. Invoices are provided in the agreed 

currency. Prices are “ex works”. Expenses for packing and freight as well as for cooling during transport are added on, including costs for 

the disposal of packaging material by the customer. Statutory value added tax is not included in the list prices. 

Payment terms: Payment obligations in countries of export must be settled within 30 days after recieving the goods. No cash discounts 

will be given unless agreed in writing. Payments by cash transfer or check are valid from the timepoint that the invoice amount is credited 

to a EUROIMMUN bank account. In cases of payment arrears, EUROIMMUN reserves the right to charge compensatory interest of 10% p. 

a., applicable from the settlement date, without any further notice. In special cases EUROIMMUN can arrange alternative payment periods 

or demand advance payments. EUROIMMUN’s demands resulting from an order cannot be offset by the customer through counter 

demands. 

Ownership rights: The delivered goods remain the property of EUROIMMUN until full payment. Selling on of EUROIMMUN products is 

only permitted for companys who are authorized in writing from EUROIMMUN to do so. Software received from EUROIMMUN should not 

be passed on to third parties without written permission from EUROIMMUN. 

Consultation: Advice from EUROIMMUN, although provided to the best knowledge, is nevertheless not binding. No liability claims can 

ensue from erroneous advice. 

Applicable law, place of jurisdiction, ineffective regulations: The contract conditions are subject to the laws of the Federal Republic 

of Germany. The United Nations Conventions on Contracts for the International Sale of Goods does not apply. The place of jurisdiction 

and fulfilment is Luebeck. If any provision of these general delivery conditions will be held invalid or unenforcable, this general delivery 

condition will not be rendered invalid as a whole, and the provisions will be changed and interpreted so as best to accomplish the objective 

of the unenforcable or invalid provision. 

— 145 —



AG 

Autoantibody Diagnostics 

acetylcholine receptor (ACHR) ...................................................................................................................12, 17., 91 

actin .......................................................................................................................... 16, 17., 34, 40, 50, 7.2, 124, 129 

adrenal cortex ................................................................................................................................13, 17., 47., 7.0, 119 

AGNA ...................................................................................................................................................................... 17. 

alpha-amylase .................................................................................................................................................98, 115 

AMA ............................................................... 6, 13, 16-17., 26, 35, 39-42, 47., 50, 7.2, 80, 82, 90, 119, 124, 127.-130 

AMPA receptor ....................................................................................................................................12, 17., 45, 121 

amphiphysin ........................................................................................................................................17., 44, 82, 120 

ANA ............................................................................. 14, 16-17., 26, 34-36, 39-40, 44, 48, 50, 7.2, 82, 89, 120-130 

ANCA ..................................................................................................12-14, 16-17., 34, 48-50, 7.0, 88, 121-123, 125 

aquaporin-4 ...................................................................................................................................12, 17., 44, 7.0, 120 

ASMA ................................................................................................................... 12, 16-17., 39-40, 7.2, 124, 128-130 

basement membrane .................................................................................. 12, 14, 16-17., 43, 7.1, 82, 88, 123, 126 

ß2-glycoprotein ................................................................................................................................................ 16, 90 

bile ducts ...........................................................................................................................................................17., 34 

BP180 ...................................................................................................................................... 12, 17., 43, 7.1, 88, 126 

BP230 ...............................................................................................................................................12, 17., 43, 7.1, 88 

BPI ..........................................................................................................................................................17., 48, 50, 88 

brain ..........................................................................................................................................................12, 119-120 

C1q .................................................................................................................................................................... 16, 90 

cANCA.................................................................................................... 12, 16-17., 34, 48, 50, 7.0, 88, 121-123, 125 

cardiolipin (AMA M1) .............................................................................................................................16-17., 86,90 

cartilage .................................................................................................................................................................. 16 

CASPR2 ..................................................................................................................................................14, 17., 45, 7.1 

cathepsin G ...........................................................................................................................................17., 48, 50, 88 

cell nuclei (ANA global test) ....................................................................................................................16, 17., 127. 

centromere ...............................................................................................................................14, 16, 34, 36, 50, 89 

cerebellum ....................................................................................................................................12-14, 44, 119, 120 

circulating immune complexes (CIC) ............................................................................................................. 16, 90 

collagen VII .......................................................................................................................13, 16-17., 43, 7.3, 116, 132 

cortisol .................................................................................................................................................................... 98 

CUZD1 (rPAg1) ..............................................................................................................................12, 17., 49, 7.1, 125 

CV2 .......................................................................................................................................................17., 44, 82, 120 

cyclic citrullinated peptide (CCP) ............................................................................................................. 16, 38, 89 

cyclin I (PCNA) ............................................................................................................ 12, 16, 26, 35, 50, 7.2, 82, 89 

cyclin II (mitosin) ....................................................................................................................................... 12, 50, 7.2 

cytoplasm of granulocytes ............................................................. 12-14, 16-17., 34, 48-50, 7.0, 88, 121-123, 125 

desmoglein ............................................................................................................................. 12, 17., 43, 7.1, 88, 126 

desmosomes .................................................................................................................................12, 17., 43, 7.1, 126 

dsDNA .........................................................................12, 16-17., 26, 34-37., 40, 44, 50, 7.2, 80, 82, 89, 91, 128, 143 

elastase ..................................................................................................................................................17., 48, 50, 88 

elastin .....................................................................................................................................................12, 16-17., 7.3 

ENA ....................................................................................................................................16, 24, 34, 36, 80, 82, 89 

endomysium...................................................................................................... 12, 17., 34, 52, 7.3, 90, 126, 130-132 

endothelial cells .............................................................................................................................12, 16-17., 34, 132 

envoplakin ...........................................................................................................................................17., 43, 88, 126 

epidermis ............................................................................................................................................ 12, 17., 7.1, 126 

EUROArray .................................................................................................................................................. 30-31, 91 

EUROPLUS ................................. 7., 12, 34, 39-40, 42-43, 48, 50, 52, 54, 56, 119, 122-124, 127., 129-133, 136, 140 

eye antigens ..........................................................................................................................................................121 

F-actin........................................................................................................................ 16, 17., 34, 40, 50, 7.2, 124, 129 

FT3 ...............................................................................................................................................................17., 42, 92 

FT4 ...............................................................................................................................................................17., 42, 92 

GABAB receptor ............................................................................................................................12, 17., 45, 7.0, 121 

GAD ..............................................................................................................................12, 17., 44, 46, 7.0, 88, 91, 119 

gangliosides ......................................................................................................................................................17., 82 

gliadin ............................................................................................ 7., 12, 17., 52, 7.3, 7.9, 98, 104, 126, 130-132, 142 

glomerular basement membrane (GBM)................................................................. 12, 17., 48, 50, 7.1, 82, 88, 123 

glutamate receptor ................................................................................................................12, 17., 45, 7.0, 120-121 

glutamic acid decarboxylase .....................................................................................12, 17., 44, 46, 7.0, 88, 91, 119 

glycine receptor ................................................................................................................................................17., 7.0 

Golgi apparatus .............................................................................................................................12, 16, 34, 50, 7.2 

goblet cells ....................................................................................................................................12, 17., 49, 7.1, 125 

GP2 (rPAg2) .........................................................................................................................................12, 17., 49, 125 

granulocyte cytoplasm ......................................................................12-14, 16-17., 34, 48-50, 7.0, 88, 121-123, 125 

heart muscle ............................................................................................................................................. 13, 17., 125 

HEp-2-cells .....................................................................6, 12-14, 34, 39-40, 44, 48, 50, 86, 120, 122-124, 126-130 

histones ................................................................................................................ 13, 16, 26, 34, -36, 50, 80, 82, 89 

Hu ...........................................................................................................................13, 17., 44-45, 7.0, 82, 86, 119-120 

HUVEC ............................................................................................................................................................ 12, 132 

hypothalamus antigens ................................................................................................................................ 13, 120 

IA-2 .........................................................................................................................................................17., 46, 88, 91 

insulin ....................................................................................................................................................17., 46, 91, 99 

intestinal goblet cells ...................................................................................................................12, 17., 49, 7.1, 125 

intrinsic factor ......................................................................................................................... 13, 17., 47., 7.1, 88, 124 

Jo-1 ............................................................................................... 13, 16, 24, 26, 34-36, 50, 7.2, 80, 82, 89-90, 127. 

keratin .......................................................................................................................... 12, 13, 16-17., 38, 43, 7.1, 126 

Ku ........................................................................................................................................13, 16, 26, 35, 50, 7.2, 82 

lactoferrin .................................................................................................................. 12, 17., 48-50, 7.0, 88, 123, 125 

LC-1 ................................................................................................................................17., 26, 36, 40-41, 80, 82, 88 

Leydig cells ...........................................................................................................................................17., 47., 7.0, 119 

LGI1 ................................................................................................................................................14, 17., 45, 7.1, 125 

liver-kidney microsomes (LKM) ........................................ 13, 17., 26, 34, 39-41, 7.1, 80, 82, 88, 119, 124, 127.-130 

liver-specific antigens ............. 12-14, 17., 26, 34, 37., 39-41, 44, 52, 68, 7.1, 80, 82, 88, 121-124, 126-127., 129-132 

LKM-1 .................................................................................................................................. 17., 26, 34, 41, 80, 82, 88 

lung alveoli ...................................................................................................................................................... 17., 123 

lymphocyte antigens ................................................................................................................................13, 17., 123 

M2 antigen (AMA-M2) ........................................................................................... 17., 26, 35, 39-41, 7.2, 80, 82, 90 

M4 antigen ......................................................................................................................................13, 17., 34, 39, 80 

M9 antigen ......................................................................................................................................13, 17., 34, 39, 80 

Ma1/Ma2 ................................................................................................................................................................. 17. 

Mab ...................................................................................................................................................... 17., 42, 7.0, 119 

MAG .......................................................................................................................................................13, 17., 44, 7.0 

Mi-2 ...........................................................................................................................................13, 16, 26, 35, 50, 82 

Microarray ................................................................................................................................................... 30-31, 91 

mitochondria (AMA) ...............................................................................13, 16-17., 39-40, 47., 50, 119, 124, 127.-130 

mitosin (cyclin II) ....................................................................................................................................... 12, 50, 7.2 

myelin ...............................................................................................................................................12-13, 17., 44, 7.0 

myeloperoxidase (MPO) .................................................................................... 13, 17., 48, 50, 80, 82, 88, 122-123 

nDNA...........................................................................12, 16-17., 26, 34-37., 40, 44, 50, 7.2, 80, 82, 89, 91, 128, 143 

nerves .............................................................................................................................................12-14, 17., 44, 120 

neuronal autoantibodies .................................................................................................................17., 44-45, 82, 86 

NMDA receptor ......................................................................................................................12, 17., 45, 7.0, 120-121 

NMO .......................................................................................................................................................... 44, 91, 120 

nRNP/Sm .............................................................................................................. 16, 24, 34-36, 50, 80, 82, 89, 127. 

nuclear membrane................................................................................................................................17., 34, 50, 7.2 

nucleosomes .................................................................................................................16, 34-35, 37., 50, 80, 82, 89 

oesophagus ................................................................................................................... 12-13, 43, 52, 126, 130-131 

ovarial antigens ........................................................................................................................................ 47., 88, 119 

P/Q calcium channel (VGCC) ................................................................................................................................. 17. 

pANCA ....................................................................................................13, 16-17., 34, 48, 50, 7.0, 88, 121-123, 125 

pancreas islets ........................................................................................................................ 14, 46-47., 7.0, 119-120 

parathyroid gland ......................................................................................................................................13, 17., 119 

parietal cells (PCA) ..........................................................................................................12, 17., 47., 7.1, 88, 119, 124 

parotid gland excretory ducts and acini ................................................................................................ 14, 17., 125 

PCA-2 ..................................................................................................................................................................... 17. 

PCNA (cyclin I) ....................................................................................................... 12, 16, 26, 34-35, 50, 7.2, 82, 89 

phosphatidylserine .......................................................................................................................................... 16, 90 

phospholipase-A2 receptor (PLA2R) .................................................................................................17., 51, 7.1, 123 

phospholipids .........................................................................................................................................16-17., 86, 90 

pituitary gland antigens ...........................................................................................................................13, 17., 120 

PL-12 ................................................................................................................................................16, 26, 35, 50, 82 

PL-7. ..................................................................................................................................................16, 26, 35, 50, 82 

placenta ......................................................................................................................................................14, 17., 119 

PM-Scl ........................................................................................................................... 16, 26, 34-36, 50, 80, 82, 89 

PNMA2 (Ma2/Ta) .........................................................................................................................................17., 44, 82 

Index 

proteinase 3 (PR3) ........................................................................................14, 17., 48, 50, 7.0, 80, 82, 88, 122-123 

renal glomeruli (GBM)............................................................................................... 12, 17., 48, 50, 7.1, 82, 88, 123 

recoverin ............................................................................................................................................................17., 82 

reticulin .......................................................................................................................................14, 17., 126, 130-132 

retina .....................................................................................................................................................13-14, 17., 121 

rheumatoid factors .................................................................................................................................... 16, 64, 90 

Ri ......................................................................................................................14, 17., 38, 44-45, 7.0, 82, 86, 119-120 

RIA .............................................................................................................................16, 32, 37., 42, 46, 88-89, 91-92 

ribosomal P-proteins......................................................................................................................14, 16, 34, 7.2, 90 

RNA-Polymerase ............................................................................................................................14, 16, 31, 34, 50 

Ro-52 ...................................................................................................................16-17., 26, 34-36, 41, 50, 80, 82, 89 

rPAg1/2 ...................................................................................................................................................... 12, 49, 125 

Sa ................................................................................................................................................................ 16, 38, 89 

Saccharomyces cerevisiae .............................................................................................15, 17., 49, 7.9, 98, 104, 125 

saliva ....................................................................................................................................................................... 98 

Scl-7.0 .................................................................................................14, 16, 24, 26, 34-36, 50, 7.2, 80, 82, 89, 127. 

skeletal muscle........................................................................................................................12-13, 17., 40, 124-125 

SLA/LP............................................................................................................................17., 26, 34, 40-41, 80, 82, 88 

Sm .......................................................................................................14, 16, 24, 26, 34-36, 50, 7.2, 80, 82, 89, 127. 

smooth muscles (ASMA) ................................................................................... 12, 16-17., 39-40, 7.2, 124, 128-130 

Sp100 ........................................................................................................................................ 17., 26, 40-41, 7.2, 82 

spermatozoa ........................................................................................................................... 14, 17., 7.0, 88, 119-120 

spindle fibers........................................................................................................................................16, 34, 50, 7.2 

SS-A ......................................................................................... 14, 16-17., 24, 26, 34-36, 50, 7.2, 80, 82, 86, 89, 127. 

SS-B ...............................................................................................14, 16-17., 24, 26, 34-36, 50, 7.2, 80, 82, 89, 127. 

ssDNA .........................................................................................................................................14, 16-17., 36, 50, 89 

striated muscles ......................................................................................................................................... 14, 40, 7.1 

TAb ....................................................................................................................................................... 17., 42, 7.0, 119 

testis ..........................................................................................................................................14, 17., 42, 47., 7.0, 119 

thrombocyte antigens ..............................................................................................................................14, 17., 123 

thyroglobulin (TG) ............................................................................................................14, 17., 42, 80, 91, 92, 119 

thyroid gland ................................................................................................... 13, 14, 17., 42, 47., 7.0, 80, 88, 91, 119 

thyroid peroxidase (TPO) ...............................................................................................................17., 42, 80, 88, 91 

titin .....................................................................................................................................................................17., 82 

Tr ............................................................................................................................................................................. 17. 

TRAb ......................................................................................................................................................17., 42, 88, 91 

transglutaminase ................................................................................................ 2, 17., 34, 52, 7.3, 90, 126, 130-132 

U1-nRNP ............................................................................................................................................... 14, 16, 7.2, 89 

vascular endothelium .................................................................................................................................16, 17., 7.3 

VGKC ....................................................................................................................................................14, 17., 45, 125 

vimentin ................................................................................................................................................ 14, 16, 50, 7.2 

Yo ...........................................................................................................................14, 17., 44-45, 7.0, 82, 86, 119-120 

zink transporter 8 ................................................................................................................................................... 17. 

zona pellucida .................................................................................................................................................. 7.0, 88 

Infectious serology 

Adenovirus ..........................................................................................................................................15, 7.7., 96, 138 

Bartonella ....................................................................................................................................15, 18, 62, 7.5, 135 

Bordetella ....................................................................................................................15, 18, 62-63, 7.3, 83, 93, 133 

Borrelia ...................................................................................... 15-18, 21, 28, 54-55, 62-63, 7.4, 83, 86-87., 93, 133 

Brucella abortus ..................................................................................................................................................... 94 

Campylobacter .............................................................................................................................15, 18, 7.3, 93, 133 

Candida ..................................................................................................................................15, 18, 62, 7.9, 111, 141 

Chikungunya virus .................................................................................................................15, 61, 7.9, 97., 141-142 

Chlamydia .................................................................................................. 15-16, 18, 60, 62-63, 7.4-7.5, 94, 134-135 

Coxsackie virus .......................................................................................................................15, 18, 62-63, 7.8, 139 

Crimean Congo fever virus ............................................................................................................... 15, 61, 7.9, 141 

Cytomegalovirus (CMV) ....................................................................................... 15, 21, 62-64, 7.6, 83, 87., 95, 137. 

Dengue virus .........................................................................................................................15, 61, 7.7., 96, 138, 141 

EBNA ............................................................................................................................ 15, 18, 56-57., 83, 97., 140-141 

EBV-CA ................................................................................................ 15, 18, 21, 56-57., 62, 64, 68, 7.8, 97., 140-141 

EBV-EA .................................................................................................................. 18, 56, 62, 64, 7.8-7.9, 97., 140-141 

Echinococcus granulosus .............................................................................................................15, 7.5, 87., 94, 136 

Echo virus ................................................................................................................................15, 18, 62-63, 7.8, 139 

Epstein-Barr virus (EBV) ...........................................15, 18, 21, 56-57., 63, 64, 68, 7.8-7.9, 83, 87., 97., 140-141, 144 

EUROPLUS ..................7., 12, 34, 39-40, 42-43, 48, 50, 52, 54, 56, 119, 122-124, 127., 129, 130-133, 136, 140-141 

EUROSORB IgG/RF absorbens ..................................................................................................................... 64, 144 

Haemophilus influenzae ...................................................................................................................... 15, 18, 62-63 

Hantavirus .............................................................................................................................. 15, 61, 7.8, 83, 97., 139 

Helicobacter pylori ...........................................................................................................15, 18, 58, 7.3, 86, 93, 133 

Herpes simplex (HSV) .......................................................................15, 18, 21, 59, 62, 7.5, 83, 87., 94-95, 136-137. 

HHV-6 ............................................................................................................................................ 15, 18, 62, 7.6, 137. 

HIV ............................................................................................................................................................... 18, 38, 62 

Influenza virus ............................................................................................................... 15, 62-63, 7.7.-7.8, 96-97., 138 

Japanese encephalitis virus .......................................................................................................15, 61, 7.7., 138, 141 

Klebsiella pneumoniae ......................................................................................................................... 15, 18, 62-63 

Legionella .....................................................................................................................15, 18, 62-63, 7.4, 93-94, 134 

Leishmania ......................................................................................................................................... 18, 61, 7.5, 136 

Listeria ......................................................................................................................................... 15, 18, 62, 7.4, 133 

Measles virus ...................................................................................................................15, 18, 21, 62, 7.6, 95, 137. 

Mumps virus ......................................................................................................…15, 18, 21, 62-63, 7.6, 95-96, 137. 

Mycoplasma ...............................................................................................................15, 18, 62-63, 7.5, 94, 135-136 

Parainfluenza virus ................................................................................................................. 15, 62-63, 7.8, 97., 139 

Parvovirus ................................................................................................................................................... 38, 83, 95 

Plasmodium ................................................................................................................................ 15, 18, 61, 136 141 

Respiratory syncytial virus (RSV) .................................................................................... 15, 18, 62-63, 7.7., 96, 138 

Rift valley fever virus................................................................................................................. 15, 61, 7.9, 139, 141 

Rubella virus .....................................................................................15, 18, 21, 62, 64, 7.6, 83, 87., 95, 98, 136-137. 

Sandfly fever virus............................................................................................................................. 15, 61, 7.8, 139 

SARS coronavirus .................................................................................................................................... 15, 61, 137. 

TBE virus ............................................................................................................... 15, 18, 21, 54, 61, 7.6-7.7., 96, 138 

Toxoplasma gondii .............................................................................................. 15, 18, 21, 62-63, 7.5, 83, 94, 136 

Treponema pallidum ..........................................................................................................15, 18, 62, 7.3-7.4, 86, 93 

Ureaplasma urealyticum ............................................................................................................................... 18, 136 

Varicella zoster virus (VZV) ........................................................................................15, 18, 21, 62-64, 7.6, 96, 137. 

VlsE ....................................................................................................................... 15, 28, 54-55, 7.4, 83, 86, 93, 133 

West Nile virus ....................................................................................................................... 15, 21, 61, 7.7., 96, 138 

Yellow fever virus ...............................................................................................................................15, 61, 7.7., 138 

Yersinia enterocolitica ...................................................................................................... 15-16, 18, 63, 87., 94, 134 

Allergology 

animal allergens ...................................................................................................................................... 19, 101-102 

environmental allergens ......................................................................................................................... 19, 115-116 

food ................................................................................................................................... 19, 66, 81, 84-85, 103-109 

further allergens....................................................................................................................................................113 

grasses ........................................................................................................................................................ 19, 66,110 

herbal and flower pollen ......................................................................................19, 66, 104-105, 107., 115, 117.-118 

house dust ....................................................................................................................................................... 19, 111 

insects ...............................................................................................................19, 41, 52, 66, 81, 85, 88-90, 97., 111 

mites ...................................................................................................................................................19, 66, 101, 111 

moulds .......................................................................................................................................................19, 111-113 

parasites ....................................................................................................................................................18, 19, 113 

pharmaceutical drugs ............................................................................................................................... 19, 99-100 

trees .......................................................................................................................................................... 19, 113-114 

Automation 

EUROBlotMaster ....................................................................................................... 26-27., 29, 35, 41, 44-45, 57.-59 

EUROIMMUN Analyzer ............................................................................................................................... 22, 66-67. 

EUROLineScan ................................................................................................ 26-29, 35, 41, 44, 55, 57.-59, 66, 143 

EUROPattern ............................................................................................................................................................. 9 

EUROStar.................................................................................................................................................................. 8 

IF Sprinter ................................................................................................................................................................. 8 

instruments .................................................................................................................................................. 8, 22, 27. 

— 147. —

One laboratory management software 

for all automated systems 



AG 

YG_0250_R_UK_B03, 10/2010 

IIFT 

ELISA 

Immunoblots 

EUROLabOffice 

EUROIMMUN AG · D-23560 Luebeck (Germany) · Seekamp 31 · Tel +49 451 58550 · Fax 5855591 · E-mail euroimmun@euroimmun.de 

D-23560 Luebeck (Germany) · Seekamp 31 · Telephone: +49 451 58550 · Fax: +49 451 5855591 · euroimmun@euroimmun.de

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