2003; baxter - Supplements - Haematologica

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68J.M.R. Saint-Remyone being to decide which epitope to use. As statedabove, the size of the T cell repertoire is suchthat a T cell can be found to any possible epitope.However, only major epitopes have to be hit, anddefining which epitope is a major one is not aneasy task. Peptides have a short half-life, so waysto increase their resistance to proteolytic enzymesand/or prolong their half-life will have to befound. Such peptides also offer the possibility toproduce variants with which it is possible tomodulate the affinity of MHC class II determinants.A special case should be made concerning regulatoryT cells, and specifically a recently identifiedsubpopulation of CD4 + T cells carrying theCD25 (IL-2) receptor, and which are activelyselected in the thymus. Such CD4 + CD25 + T cellsexert their regulatory properties by a combinationof mechanisms including secretion of suppressivecytokines such as IL-10 and TGF-β andcell-to-cell contact. It is too early to decidewhether such regulatory T cells will be useful ineliminating FVIII inhibitors, but we can alreadyanticipate a number of studies in this direction.Perhaps the ultimate goal in the therapy ofFVIII inhibitors would be to eliminate FVIII-specificimmunocompetent cells. Actual deletion ofB and T cells occurs as part of the homeostasis ofthe immune system. Deletion occurs as a resultof either neglect or overstimulation. An immuneresponse is triggered only whenever there is asubtle equilibrium between activation and suppressionsignals. If activation goes too far, thenspecific B as well as T cells are eliminated. Thebest example of this is the so-called activationinducedcell death, which drives T cells into committingsuicide via the overexpression of FAS andFas-ligand. It is however too early to decidewhether it would be possible to master such aphenomenon for therapeutic purposes. One mayperhaps argue that treating patients withinhibitor by infusing large doses of FVIII alreadyrepresents an example of specific T cell deletion.Experiments are ongoing to determine whetherthis is the case.This short overview of the prospects forimmune therapy of FVIII inhibitors should leavethe reader with the strong feeling that many possibilitiesexist, which, within the forthcoming tenyears, should be reducible to practice.haematologica vol. 88(supplement n. 12):september 2003
[New Aspects in Treatment of Hemophilia B Patients]review paperImmune tolerance induction inhemophilia B. Internationalimmune tolerance registryhaematologica 2003; 88(suppl. n. 12):69-70http://www.haematologica.org/free/immunotolerance2001.pdfI. WARRIERDivision of Hematology/Oncology, Children's Hospital ofMichigan, Wayne State University School of Medicine,Detroit, Michigan, USAFIX inhibitorsUnlike FVIII inhibitors in hemophilia A ourknowledge about FIX inhibitors in hemophilia Bis limited. The main reason for this is the smallernumber of severe FIX deficient patients.Inhibitor development is also less common withFIX deficiency. 1,2 In addition, anaphylaxis occurringsimultaneously with inhibitor developmentis a unique problem receltly described in hemophiliaB patients. 3 Since the last ITSG (immunetolerance study group) meeting in Palermo, Sicily,we have developed a FIX inhibitor registryfrom, which is available on the ISTH web site orcan be obtained by calling 1.888.877.0767. Thedata presented here is obtained from several publishedreports and questionnaires in addition tothe registry. 4,5When one looks at the data presented in Table1, it is apparent that FIX inhibitor patients withallergywere selectively reported to the registryand not all patients with hemophilia B andinhibitors. Thirty of the 46 patients withinhibitors and allergy had provided informationdetailing inhibitor development (Table 2). Someof the other features included: i)affection of allethnic and racial groups and ii) reported use ofvarious factor concentrates including PCC,APCC, monoclonal FIX, and rFIX at the time ofinhibitor development and allergy.Immune tolerance inductionExperience with ITI in hemophilia B inhibitorpatients is limited due to low prevalence, thrombogenicityof PCC and APCC, unavailability ofultrapure products until recently and finally lackof a standard method for ITI.From the limited information available, ITI hasbeen attempted in 21/30 patients (70%). ITIwas successful in only 2/21 patients (9.5%).Several different protocols were used for ITIincluding some with plasmapheresis and treatmentwith cyclophosphamide and IVIG.The only published data regarding ITI in hemo-Table 1. Inhibitors in hemophilia B.Total number of inhbitors 81In USA 52Outside USA 29Inhibitors with allergy 46In USA 24 (46%)Outside USA 22 (76%)Table 2. Characteristics of FIX inhibitor patients.Median age at INH 19.5 months (9-156 months)Median exposure days prior to INH 11 days (2-180 days)Peak inhibitor titer 30 BU (1-950 BU)Complete gene deletion 50%philia B patients without allergy comes from Dr.Berntrop’s Treatment Center and he will be discussingthat in his paper. A unique complicationof ITI seen in hemophilia B inhibitor patientswith allergy is the development of NephroticSyndrome during ITI. 6 This will be discussed indetail by Dr. Bruce Ewenstein.The genetics of inhibitor development inhemophilia B will be discussed by Dr. Lillicrap inhis paper. I will end my short report with a pleato hemophilia treaters for reporting all thehemophilia B inhibitor patients to the InternationalImmune Tolerance Registry. The toll freenumber for the Registry is 1.888.877.0767.References1. Briët E. Factor IX inhibitors in hemophilia B patients:their incidence and prospects for development withhigh purity FIX products. Blood Coagul Fibrinolysis1991; Suppl 2:47-50.haematologica vol. 88(supplement n. 12):september 2003
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2003; baxter - Supplements - Haematologica

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