Check GAD antibody positivity with the Diamyd anti-GAD RIA plate*

GAD in GraphsImmune deviation of T cell responsesto GAD65 inhibits disease progressionand protects islet transplantsin NOD mice100GAD Peptides and T1DM-Associated HLA MoleculesMay Hold the Key to DiseasePrediction and PreventionC.B. TSanjeevi1DM is an autoimmune diseasewhich occurs predominantlyin children.Autoantibodies to T1DMautoantigens (GAD65 orGlutamic acid decarboxylaseisoform 65, IA-2 or Tyrosine phosphatase andinsulin) are used to identify ongoing autoimmuneprocess both in newly diagnosed T1DM childrenand prediabetic individuals. The autoreactive Tcells are implicated in the destruction of the insulinproducing beta cells leading to the disease andthe autoantibodies are considered only markersfor the disease.We have studied HLA-DQ that is associatedwith T1DM in my laboratory. These studies havehelped us to identify naturally processed and presentedpeptides from susceptible and protectiveHLA-DQ, sequence these peptides and show thebinding motifs (from peptide sequencing andmolecular modelling).We have screened the diabetes autoantigenGAD65 and identified several 15 amino acid longpeptides that carry the right binding motifs forHLA-DQ associated with T1DM.We believe that T cells reacting to the DQrestricted peptides from T1DM autoantigen(GAD65) are in the peripheral blood of newlyCarani B. Sanjeevi isan Associate Professorin the division ofDiabetes andEndocrinology at theDepartment ofMolecular Medicine atthe KarolinskaInstitute in Stockholm. Sanjeevi is also headat the ‘Molecular Immunogenetics’ researchgroup at Karolinska Hospital. Sanjeevi isassociated with his contribution of MHC inautoimmune Diabetes and is currently workingon the role of peptides from diabetesautoantigens (GAD65) and viruses that carrymotifs for diabetes associated HLA-DQ, indisease prediction.diagnosedT1DM childrenand prediabeticchildren andtheir detectionis predictive ofthe disease.An assay toidentify the Tcells reacting tothe DQ restrictedpeptides hasbeen standardizedand is being tested in newly diagnosed Type 1diabetes children and their first degree relatives. Wehope that this assay will help us to both diagnosethe disease and also to predict the disease in firstdegree relatives.Our subsequent aim would be to use these peptidesin some form of peptide-based vaccine approach.Future potential for GAD65:GAD65 has a very good potential in the diagnostic,predictive as well as preventive approach. The keyis to find the form in which GAD65 could beused to achieve the goals. It could be wholeGAD65 or modified GAD65 or peptides fromGAD65.Diabetes Incidence (%)% Diabetes Recurrence1008060402080604020§-GAL.Insulin B-chainHSP277GAD6500 15 30 45 60 75 90 105Post-transplantation Time (days)Tian et al. (1996) Modulating autoimmuneresponses to GAD inhibits disease progressionand prolongs islet graft survival in diabetespronemiceNature Medicine 2:1348-1353• Pancreatic islets transplantedinto diabetic NOD mice that hadbeen pretreated with GAD65survived longer than in those thathad been pretreated with eitherß-galactosidase, insulin B chainor hsp65• GAD65 treatment increases islettransplant efficacyNasal administration of GAD65 preventsdiabetes in NOD miceGAD65 peptidesControl peptide010 15 20 25 30 35 40 45 50 55 60Time (weeks)Tian et al. (1996) Nasal administration of glutamatedecarboxylase (GAD65) peptides inducesTh2 responses and prevents murine insulindependentdiabetesJ Exp Med 183:1561-1567• Intranasal administration ofGAD65 peptide into 2-3wk old NODmice induced IgG1 anti-GAD antibodies,reduced IFN-γ and increasedIL-5responses to GAD65 (i.e. diversion ofthe GAD response from Th1-Th2)• Nasal administration ofGAD65 prevents diabetesdmccad june 2003page 27