Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in both Australians and Asians with type 1 (insulin-dependent) diabetes mellitus.
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)
John Curtin School of Medical Research, Australian National University, Canberra.
S W
SW
Serjeantson
M R
MR
Kohonen-Corish
M J
MJ
Rowley
I R
IR
Mackay
W
W
Knowles
P
P
Zimmet
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000032:analysis* / Q000235:genetics; D000917:Antibody Formation; D044466:Asian People / Q000235:genetics*; D001315:Australia / Q000453:epidemiology; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007723:Korea / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length; D044465:White People / Q000235:genetics*
D000906:Antibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D005968:Glutamate Decarboxylase