HLA CLASS-II IS ASSOCIATED WITH THE FREQUENCY OF GLUTAMIC-ACID DECARBOXYLASE-M, 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 m ellitus (type 1), while the type 1-associated HLA haplotypes differ. I n 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% slo wly progressive type 1, 3% type 2 patients, and 1.7% healthy individua ls. In 75 HLA-typed type 1 patients, the GAD65Ab frequency was higher in short-duration patients with DRB108 allele (100%, Pc<0.05). GAD65A b frequencies in DQB10302, DQB1*0303, and DRB1*09-positive, long-dura tion type I patients were lower than those in short-duration type I pa tients (14%, 19%, and 20%, Pc<0.02 compared with short-duration type 1 , 90%, 75%, and 71%, respectively), while the frequency varied less in DQB104 individuals (44% and 30% in short- and long-duration type 1 p atients, respectively). These findings were also observed among patien ts with DRB104, i.e., the haplotype DRB1*0405-DQB1*0401 showed less v ariation in frequency of GAD65Ab (44% and 35% in short- and long-durat ion type 1 patients, respectively), while DRB104xx-DQB1*0302 showed l ower frequency in long-duration type 1 than short-duration (13% and 10 0%, respectively). Thus, HLA class II is associated with frequency GAD 65Ab, and this association might be affected by disease duration in Ja panese type 1 patients.