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).
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