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 (GADA) and IA-2 (IA-2A) in patients with type 1 and type 2 diabetes.


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.
Hawa
M I
MI
Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, UK. m.i.hawa@mds.gmw.ac.uk
Fava
D
D
Medici
F
F
Deng
Y J
YJ
Notkins
A L
AL
De Mattia
G
G
Leslie
R D
RD
D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D005060:Europe / Q000208:ethnology; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood*; D007527:Isoenzymes / Q000276:immunology*; D012016:Reference Values; D014430:Twins, Monozygotic; D044465:White People
D001323:Autoantibodies; C096322:ICA512 autoantibody; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007527:Isoenzymes; D007073:Immunoglobulin E; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2