Seventy IDDM patients (insulin-dependent diabetics), 48 females and 22 males, most of them adults at the onset of diabetes, and suffering from at least one other associated autoimmune manifestation (AAM) were studied for HLA A,B,C, DR markers and Bf, C4 complement components. Comparisons were made with 108 normal controls and a series of 287 IDDM patients with juvenile onset (under 25 years) and no patent other autoimmune disease. The increase in frequency of HLA-B8 among IDDM patients with AAM was confirmed (36% versus 20% in controls) (p less than 0.04). The frequency of DR4 among diabetics with AAM (33%) was not significantly different from the normal frequency (27%), and the allelic combination DR3/4 was found in only 13% of IDDM with AAM. Corresponding frequencies in patients with IDDM alone were 66% for DR4 and 34% for DR3/4 (p less than 10(-6) and 10(-3) respectively). These results confirm the heterogeneity of IDDM and support, by genetic arguments, the concept of overlapping entities. The hypothesis of a common background of autoimmunity associated with B8 DR3 can be postulated, while the organ specific target process should be associated with various DR alleles.
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