Studies of autoantibodies reactive with thyroid membrane antigens and insulin in non obese diabetic mice

Enzyme-linked immunosorbent assay (ELISA) was used to study the temporal relationship between the appearance of murine autoantibodies reactive to insulin and thyroid membrane antigens (TMA) and the development of diabetes and thyroiditis in the non obese diabetic (NOD) mouse. Overall, 28% of NOD mice had antibodies specific for mouse thyroid membrane antigens (MTMA), 30% had antibodies to human thyroid membrane antigens (HTMA) and 23% of NOD mice had insulin autoantibodies (IAA), in at least one of their serial monthly blood samples. Non autoimmune BALB/c mice did not develop antibodies to these antigens. Presence of IAA was associated with the development of diabetes and in 87% of cases such antibodies were detected before the diabetes was diagnosed. IAA were usually demonstrated before insulitis. No association between thyroiditis and IAA was noted. Anti-MTMA and anti-HTMA antibodies were detected more frequently in NOD mice with thyroiditis than in those without thyroid inflammation. No significant association was noted between detection of serum anti-TMA antibodies and the development of diabetes. In young mice, anti-TMA antibodies were not detected in the absence of thyroiditis. Western blot analysis of NOD sera positive for MTMA by ELISA revealed a heterogeneous pattern of reactivity. The significance of these findings with respect to the pathogenesis of diabetes and thyroiditis and their association, is discussed.