Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM).

Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. This assay showed that sensitivity and specificity were 83.3% and 100%, respectively. GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. GAD65 antibodies were detected in none of 25 patients with NIDDM or 25 healthy volunteers. The correlation between GAD65 antibodies and ICA, and 64K antibodies was observed to be significant (r = 0.60, P = 0.0003 and r = 0.47, P = 0.007, respectively). GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM.