HLA class II is associated with the frequency of glutamic acid decarboxylase M r 65 000 autoantibodies in Japanese patients with insulin-dependent diabetes mellitus

Autoantibodies to glutamic acid decarboxylase (GAD65Ab) are common in both caucasian and Japanese patients with insulin-dependent diabetes mellitus (type 1), while the type 1-associated HLA haplotypes differ. In the present study, we analyzed GAD65Ab in relation to HLA-DQ and-DR alleles in Japanese type 1 patients. GAD65Ab were found in 58% short-duration (less than 5 years) type 1,23% long-duration type 1,56% slowly progressive type 1,3% type 2 patients, and 1.7% healthy individuals. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB1^*08 allele (100%,Pc<0.05). GAD65Ab frequencies in DQB1^*0302, DQB1^*0303, and DRB1^*09-positive, long-duration type 1 patients were lower than those in short-duration type 1 patients (14%, 19%, and 20%,Pc<0.02 compared with short-duration type 1, 90%, 75%, and 71%, respectively), while the frequency varied less in DQB1^*04 individuals (44% and 30% in short- and long-duration type 1 patients, respecitively). These findings were also observed among patients with DRB1^*04, i.e., the haplotype DRB1^*0405-DQB1^*0401 showed less variation in frequency of GAD65Ab (44% and 35% in short- and long-duration type 1 patients, respectively), while DRB1^*04xx-DQB1^*0302 showed lower frequency in long-duration type 1 than short-duration (13% and 100%, respectively). Thus, HLA class II is associated with frequency GAD65Ab, and this association might be affected by disease duration in Japanese type 1 patients.