Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with type 1 (insulin-dependent) diabetes mellitus

Diabetologia. 1992 Oct;35(10):996-1001. doi: 10.1007/BF00401432.

Abstract

Antibodies to glutamic acid decarboxylase, previously known as the 64 kD antigen, appear to be more predictive of Type 1 (insulin-dependent) diabetes mellitus in Caucasoids than other autoantibodies to islet cell antigens. However, seropositivity to glutamic acid decarboxylase is not universal at the onset of Type 1 diabetes and the prevalence in Asians is low compared to Caucasoid patients. This suggests the involvement of multiple pancreatic autoantigens in the Type 1 diabetes autoimmune process or, genetic differences within and between ethnic groups that contribute to the heterogeneous autoimmune response to glutamic acid decarboxylase or both. Alternatively some cases of Type 1 diabetes could have an aetiology unrelated to autoimmunity. This study examined the differential response to glutamic acid decarboxylase according to HLA-DR and -DQ genotypes, as determined by RFLP, in 49 white Australian and 44 Asian patients with Type 1 diabetes. Among Australians heterozygous for HLA-DR3, DR4, 85% were positive for antibodies to glutamic acid decarboxylase, significantly different (p = 0.039) from the prevalence of 48% in patients with at least one HLA-DR antigen other than DR3 or DR4. Also, among Australians, the presence of "low risk" HLA-DQ antigens, namely DQw5, DQw6 or DQw7, reduced the prevalence of antibodies to glutamic acid decarboxylase by 40% (p = 0.064). Among Asians with Type 1 diabetes and with antibodies to glutamic acid decarboxylase, HLA-DR9 was significantly (p = 0.037) increased in frequency, at 63% compared with 22% in those without glutamic acid decarboxylase antibodies, and the presence of a "low risk" HLA-DQ allele reduced the antibody rates by 87% (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / analysis*
  • Antibodies / genetics
  • Antibody Formation
  • Asian Continental Ancestry Group / genetics*
  • Australia / epidemiology
  • Biomarkers / analysis
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • European Continental Ancestry Group / genetics*
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / immunology*
  • HLA-DQ Antigens / analysis
  • HLA-DQ Antigens / genetics
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / genetics*
  • Hong Kong / epidemiology
  • Humans
  • Japan / epidemiology
  • Korea / epidemiology
  • Polymorphism, Restriction Fragment Length

Substances

  • Antibodies
  • Biomarkers
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Glutamate Decarboxylase