IgG subclass antibodies to glutamic acid decarboxylase and risk for progression to clinical insulin-dependent diabetes

Hum Immunol. 1998 Aug;59(8):493-9. doi: 10.1016/s0198-8859(98)00040-8.


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.

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / analysis
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glutamate Decarboxylase / immunology*
  • Histocompatibility Testing
  • Humans
  • Immunoglobulin G / analysis*
  • Insulin / immunology
  • Islets of Langerhans / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors


  • Autoantibodies
  • Immunoglobulin G
  • Insulin
  • Glutamate Decarboxylase