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

S. W. Serjeantson, M. R J Kohonen-Corish, M. J. Rowley, I. R. Mackay, W. Knowles, P. Zimmet

Research output: Contribution to journalArticle

53 Citations (Scopus)

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). These observations may reflect differential genetic/environmental interactions in Type 1 diabetes or differential persistence of glutamic acid decarboxylase antibodies in those with different genetic backgrounds.

LanguageEnglish
Pages996-1001
Number of pages6
JournalDiabetologia
Volume35
Issue number10
DOIs
Publication statusPublished - 1 Oct 1992

Keywords

  • Glutamic acid decarboxylase
  • HLA-DQ
  • HLA-DR
  • Hong Kong
  • Japan
  • Korea
  • Type 1 (insulin-dependent) diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Serjeantson, S. W. ; Kohonen-Corish, M. R J ; Rowley, M. J. ; Mackay, I. R. ; Knowles, W. ; Zimmet, P. / Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus. In: Diabetologia. 1992 ; Vol. 35, No. 10. pp. 996-1001.
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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). These observations may reflect differential genetic/environmental interactions in Type 1 diabetes or differential persistence of glutamic acid decarboxylase antibodies in those with different genetic backgrounds.",
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Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus. / Serjeantson, S. W.; Kohonen-Corish, M. R J; Rowley, M. J.; Mackay, I. R.; Knowles, W.; Zimmet, P.

In: Diabetologia, Vol. 35, No. 10, 01.10.1992, p. 996-1001.

Research output: Contribution to journalArticle

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T1 - Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with Type 1 (insulin-dependent) diabetes mellitus

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AB - 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). These observations may reflect differential genetic/environmental interactions in Type 1 diabetes or differential persistence of glutamic acid decarboxylase antibodies in those with different genetic backgrounds.

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