ASSOCIATION BETWEEN ANTIBODIES TO THE MR-67,000 ISOFORM OF GLUTAMATE-DECARBOXYLASE (GAD) AND TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS WITH COEXISTING AUTOIMMUNE POLYENDOCRINE-SYNDROME TYPE-II

By using an immunoprecipitation assay, we analysed reactivity of autoa ntibodies to human recombinant GAD(65) and GAD(67) in sera from patien ts with autoimmune polyendocrine syndrome Type II (APS II) with and wi thout Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. Overall antibodies to GAD(6 5) were correlated with IDDM in all study groups, whereas GAD(67) anti bodies were associated with IDDM when APS II coexists. Antibodies to G AD(65) and GAD(67) were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). In short-sta nding IDDM (<1 year), antibodies to GAD(67) were significantly more fr equent in patients with APS II (5 of 9 [55.6%] subjects) compared to m atched diabetic patients without coexisting polyendocrinopathy (1 of 1 8 [5.6%] subjects) (p < 0.02). The levels of GAD(65) (142+/-90 AU) and GAD(67) antibodies (178+/-95 AU) were significantly higher in patient s with polyglandular disease than in patients with isolated IDDM (91+/ -85 AU and 93+/-57 AU) (p < 0.02). Interestingly, all 11 GAD(67) antib ody positive subjects also had GAD(65) antibodies (p < 0.0001), and in 10 of 11 anti-GAD(67) positive sera the GAD(67) antibodies could be b locked by either GAD(67) or GAD(65), suggesting the presence of cross- reactive autoantibodies. No correlation was observed between GAD antib odies and age, sex or any particular associated autoimmune disease, be sides IDDM. GAD antibodies were present in only 1 of 6 (16.7%) patient s with APS Type I, in 1 of 26 (3.9%) patients with autoimmune thyroid disease but in none of the patients with Addison's disease (n = 16), p ernicious anaemia (n = 7) or normal controls (n = 50). Our data sugges t distinct antibody specificities reactive to GAD isoforms in APS II a nd IDDM, which might reflect different mechanisms of autoimmune respon se in IDDM with coexisting autoimmune polyendocrine autoimmunity.