HUMAN LYMPHOCYTE ANTIGENS IN GRAVES-DISEASE - CORRELATION WITH PERSISTENT COURSE OF DISEASE

Graves' disease is a thyroid autoimmune disorder associated with speci fic human lymphocyte antigen (HLA) alleles, characterized by an unpred ictable long-term course. To investigate possible relations between HL A phenotype and outcome of the disease, the authors typed for HLA anti gens in 105 patients with Graves' disease with different course of dis ease. Al]. patients were treated with antithyroid drugs for at least 1 2 months; 29 patients had stable remission 24 or more months after wit hdrawal of treatment; 76 patients had persistent disease-66 unremittin g/relapsing hyperthyroidism, 10 stable hypothyroidism-36 or more month s after onset of disease. The following findings emerged from this stu dy: 1) HLA B8 and DR3 were increased significantly in Graves' patients versus 6,682 control subjects from the same geographic area (23.80% v s 12.01%, odds ratio [OR] 1.98, and 31.43% vs 18.00%, OR 1.75, respect ively); the antigen combinations B8-DR3, B8-Cw7-DR3, and A1-B8-Cw7-DR3 were significantly more frequent in Graves' patients vs control subje cts; in addition, these combinations were present exclusively in patie nts with persistent disease (B8-DR3 28.95%, OR 7.14, B8-Cw7-DR3 27.63% , OR 11.24, and A1-B8-Cw7-DR3 18.42%, OR 11.29). These data provide ev idence that not only susceptibility to Graves' disease, but also persi stent activity of the autoimmune process, producing either hyperthyroi dism or stable hypothyroidism, is associated with specific HLA antigen phenotypes.