1. Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality.
- Author
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Hawa, Mohammed I., Fava, Danila, Medici, Francesco, Deng, Yang-Jia, Notkins, Abner L., De Mattia, Giancarlo, Leslie, R. David G., Hawa, M I, Fava, D, Medici, F, Deng, Y J, Notkins, A L, De Mattia, G, and Leslie, R D
- Subjects
THERAPEUTIC use of immunoglobulins ,GLUTAMATE decarboxylase ,DIABETES ,IMMUNOLOGY ,AGE factors in disease ,AUTOANTIBODIES ,COMPARATIVE studies ,ENZYMES ,IMMUNOGLOBULINS ,TYPE 1 diabetes ,ISOENZYMES ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,TYPE 2 diabetes ,REFERENCE values ,RESEARCH ,TWINS ,WHITE people ,EVALUATION research - Abstract
Objective: To determine the isotypes and clonality of antibodies to GAD (GADA) and IA-2 (IA-2A) in patients with type 1 and type 2 diabetes.Research Design and Methods: We studied the following consecutive series of patients who attended a diabetes center for antibodies to GADA and IA-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 patients with type 1 diabetes (15 of whom developed diabetes) who were followed prospectively.Results: GADA or IA-2A were detected in 37 (71%) type 1 diabetic patients compared with only 10 (5%) type 2 diabetic patients (P<0.0001). Both GAD and IA-2 antibodies, regardless of the type of diabetes, were usually subclass restricted to IgG1 and were polyclonal. IgM, IgG3, and IgE isotypes were also detected, but all isotypes of GADA and IA-2A were less prevalent than IgG1 (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-specific antibodies in type 1 and type 2 diabetes is similar and probably involves a chronic nonrandom antigen-driven polyclonal B-cell activation that is consistent with a Th1-type immune response. [ABSTRACT FROM AUTHOR]- Published
- 2000
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