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Certain class II determinants of the human histocompatibility locus antigens (HLA) have been implicated in the aetiology of several autoimmune diseases, including rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM). HLA-Dw4 was the first HLA determinant found to be significantly increased in RA patients compared with controls, while Dw4 and Dw3 were found to be significantly increased in IDDM patients. When the HLA-DR system was defined, RA patients were found to have an increased frequency of DR4 and IDDM patients an increased incidence of both DR4 and DR3 compared with controls. As the HLA-Dw specificities are narrower than the serologically defined DR specificities, it was of specific interest to the present study that Dw4, Dw10, Dw13, Dw14, Dw15 and DKT2 are included in DR4. We describe here new restriction fragment length polymorphisms (RFLPs) and, together with the newly described serologically defined DQ specificity TA10, test their prevalence and associations in controls and diseased patients. We find that the newly characterized DNA bands are present at a much higher frequency in RA and IDDM patients than in controls. These findings may lead to a greater understanding of the pathogenesis of such diseases.

HLA-D specificities have been investigated in 58 classical Type 1 diabetics and 43 healthy subjects. Both groups were selected according to the HLA-B locus antigens which are known to have a significant positive or negative association with the disease. The results indicate that (1) the primary association of the disease is with HLA-DW3, (2) the increased frequency of DW4 in diabetics with rare exception is co-existent with the presence of DW3, (3) the low frequency of DW2 is secondary to the increase in DW3 and/or DW4, and is not consistent with a primary 'protective' role. It is suggested that these data support the hypothesis of interaction between HLA-linked genes operating by separate mechanisms to confer the susceptibility to young onset Type 1 diabetes (Type 1 A).