Ia-Type alloantigens and humoral autoimmune responsiveness in insulin-dependent diabetes mellitus.

In the search for markers either closely linked to or identical with the hypothetical "diabetogenic major histocompatibility gene," immune region-associated alloantigens were defined in 80 patients with insulin-dependent diabetes and in 107 controls. A close association between the Ia-type alloantigen DRw3 and DRw4 and insulin-dependent diabetes was obtained. DRw3 was found in 36% and DRw4 in 32% of the patients compared to 11% and 16%, respectively, of the controls. In addition, a significant influence of DRw3 and humoral anti-islet-cell autoimmunity could be observed, which was found to be due to a high incidence of DRw3 in those patients with islet cell antibody persistence. Islet-cell antibodies (ICA) were observed in 60% of the DRw3-positive patients compared to only 9% of the DRw3-negatives with longstanding disease (greater than 5 yr). These data show a significant association between insulin-dependent diabetes and the Ia-type alloantigens DRw3 (p uncorr. less than 0.0005) and DRw4 (p uncorr. less than 0.025). Furthermore, they provide direct evidence of an association between an Ia-type alloantigen and persisting humoral autoimmune responsiveness in man.