HLA and Graves' Disease: An Association with HLADRw3

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Abstract
HLA-A, -B and -C antigens were tested by a standard lymphocyte microcytotoxicity technique in 86 Caucasian patients from western France with Graves'' disease, and the data were compared with findings in 356 healthy controls. For HLA-DR antigen typing performed by lymphocyte microcytotoxicity testing using a long incubation time, the data were compared to findings in 100 healthy controls. An increase was found in the frequency of HLA-DRw3 (51.16% of patients vs. 20% of controls, corrected P (Pc) < 0.0003; relative risk (rr), 4.19) associated with an increased frequency of HLA-B8 (44.19% of patients vs. 22.47% of controls; Pc < 0.001; rr, 2.73) and HLA-A1 (40.7% of patients vs. 28.93% of controls; Pc < 0.03; rr, 1.71). A diminished frequency was found for HLA-B12 (12.79% vs. 31.74%; Pc < 0.01). The antigen combination B8-DRw3 was noted in 37 of the 86 Graves'' disease patients compared with 13 of 100 controls (Pc < 0.00003). No association was observed between HLA antigens and the different manifestations of the disease, e.g., the presence of goiter and/or exophthalmos, or the severity of clinical or biochemical signs. The present findings confirm the reported increase in the frequency of HLA-B8 in patients with Graves'' disease. The most striking findings was the prevalence of HLA-DRw3, which, with recent reports on lymphocyte-defined D locus determinants pointing to an increased frequency of HLA-Dw3, suggests that the gene or genes conferring susceptibility to Graves'' disease may be located close to the HLA-D (DR) region of the 6th chromosome.