IgG subclass antibodies to glutamic acid decarboxylase and risk for progression to clinical insulin-dependent diabetes.
Pancreatic islet beta cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is believed to be mediated by a T-helper 1 (T(H)1) lymphocyte response to islet antigens. In the mouse, T(H)1 (IL-2, IFN-gamma) and T(H)2 (IL-4, -5, -6, -10) responses are associated with the generation of IgG2a and IgG1 subclasses, respectively. The equivalent human subclasses have not been defined. Because the IgG subclass response to an antigen may be a potentially useful marker of T(H)1/T(H)2 immune balance we measured IgG subclass antibodies to glutamic acid decarboxylase (GAD), a major islet autoantigen in IDDM, in 34 newly-diagnosed IDDM patients and in 28 at-risk, first-degree relatives of people with IDDM. In the newly-diagnosed patients, total IgG antibodies to GAD were detected in 74% (25/34); IgG1 and/or IgG3 were significantly more frequent than IgG4 or IgG4/IgG2 (14/34 versus 5/34, p = 0.01). GAD antibody-negative patients were significantly younger (p = 0.01). In 15 at-risk relatives who had not progressed to clinical diabetes after a median of 4.5 years, 10 had IgG2 and/or IgG4 antibodies compared to only 3/13 progressors (p = 0.02). Total IgG and IgG2 antibodies were higher in non-progressors. Non-progressors were older than progressors (p = 0.01), and relatives with IgG2 and/or IgG4 responses were also older (p = 0.01). These results suggest that IgG subclass antibodies to GAD may contribute to diabetes risk assessment in islet antibody relatives.
Couper
J J
JJ
Department of Endocrinology, Women's and Children's Hospital, South Australia, Australia.
Harrison
L C
LC
Aldis
J J
JJ
Colman
P G
PG
Honeyman
M C
MC
Ferrante
A
A
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
D001323:Autoantibodies; D007074:Immunoglobulin G; D007328:Insulin; D005968:Glutamate Decarboxylase