Relationship between T and B Cell Responses to Proinsulin in Human Type 1 Diabetes

• Published in: Annals of the New York Academy of Sciences 2003-11, Vol.1005 (1), p.288-294
• Main Authors: DURINOVIC-BELLÓ, IVANA, MAISEL, NICOLA, SCHLOSSER, MICHAEL, KALBACHER, HUBERT, DEEG, MARTIN, EIERMANN, THOMAS, KARGES, WOLFRAM, BOEHM, BERNHARD O.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; autoantibodies; Autoantibodies - blood; B-Lymphocytes - immunology; Child; Child, Preschool; cytokines; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; insulin; Middle Aged; proinsulin; Proinsulin - immunology; T cells; T-Lymphocytes - immunology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1288.045

: In type 1 diabetes, humoral and cell‐mediated responses to insulin and proinsulin are detectable. Autoantibodies to insulin are associated with impending disease in young individuals and are used as predictive markers to determine disease risk. The aim of this study was to investigate whether different cytokine patterns of cellular reactivity to insulin might serve as additional specific markers of disease maturation and might improve disease prediction in individuals at risk. We correlated T and B cell responses to insulin in subjects with increased genetic risk (HLA‐DRB1*04, DQB1*0302) for diabetes with or without islet autoantibodies (Ab+ subjects and controls, respectively) and HLA‐matched patients. Peripheral blood mononuclear cells were stimulated with 15 overlapping proinsulin peptides (16‐mer), and proinflammatory Th1 (IFNγ) and anti‐inflammatory Th2 (IL‐4) cytokines were analyzed. We observed a simultaneous increase in IL‐4 and IFNγ secretion in early islet autoimmunity of Ab+ subjects, but not in insulin‐treated T1D patients. Furthermore, the increase in IL‐4 secretion in Ab+ subjects was associated with insulin autoantibody responses. There was no correlation of either IFNγ or IL‐4 secretion with insulin antibody responses in patients already treated with exogenous insulin. In conclusion, our findings reveal that quantification of cytokine responses to proinsulin in peripheral blood may prove to be a promising specific marker of diabetes progression and could, in addition to insulin autoantibodies, be used in the prediction of type 1 diabetes.