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

Abstract

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, respectively). 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.