Clinical and immunologic studies of HLA-DR typed insulin-dependent diabetics--a mini-review

There is strong association between insulin-dependent (type I) diabetes and the HLA DR3 and/or DR4 factors. Also, evidence has been accumulated that an immune response gene associated to the DR3 region may be a denominator for the development of an endocrine autoimmunity. It is particularly the late onset type I diabetes that belongs to the so-called "primary" autoimmune variety and also shows an increased tendency for the development of other autoimmune disorders. HLA DR 3 and/or HLA DR 4 associated mechanisms seem to influence a variety of clinical and immunologic findings in type I diabetes. Basically, this concept is supported by findings on seasonal variations in diabetes manifestation, on viral antibodies, on anti-insulin antibody formation, and on the natural course of endogenous insulin secretion in relation to HLA haptotypes . There are, however, conflicting data concerning islet cell antibodies, circulating immune complexes, and the incidence of diabetic microangiopathy in relation to the HLA-system. Many of these findings may be explained on the basis of an HLA heterogeneity. But this does not necessarily point to an etiological genetic heterogeneity of type I diabetes.