Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes - Isotype restriction and polyclonality

OBJECTIVE - To determine the isotypes and clonality of antibodies to GAD (G ADA) and 1A-2 (1A-2A) in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS - We studied the following consecutive series o f patients who attended a diabetes center for antibodies to GADA and 1A-2A: 52 newly diagnosed type 1 diabetic patients, 199 type 2 diabetic patients, 200 control patients, and a cohort of 34 nondiabetic identical twins of pa tients with type 1 diabetes (15 of whom developed diabetes) who were follow ed prospectively RESULTS- GADA or 1A-2A were detected in 37 (71%) type 1 diabetic patients c ompared with only 10 (5%) type 2 diabetic patients (P < 0.0001). Both GAD a nd 1A-2 antibodies, regardless of the type of diabetes, were usually subcla ss restricted to IgG1 and were polyclonal. IgM, IgG3, and IgE isotypes were also detected, but all isotypes of GADA and 1A-2A were less prevalent than IgG 1 (P < 0.017 for either antibody), There was no evidence of spreading or switching of isotypes before the onset of type 1 diabetes. CONCLUSIONS - These observations suggest that the pathogenesis of antigen-s pecific antibodies in type 1 and type 2 diabetes is similar and probably in volves a chronic nonrandom antigen-driven polyclonal B-cell activation that is consistent with a Th1-type immune response.