RELATIONSHIP BETWEEN HLA ANTIGENS AND INFECTIOUS AGENTS IN CONTRIBUTING TOWARDS THE DEVELOPMENT OF GRAVES-DISEASE

Graves' disease (GD) is an autoimmune thyroid disorder which is associ ated with the human leucocyte antigens HLA-DR3 and DQA1 O501 in Cauca sians. We have explored the possibility that some patients with certai n HLA specificities develop anti-HLA antibodies which are correlated w ith environmental factors that may contribute to the development of GD . We studied 40 GD patients and 157 healthy individuals (controls). Se rology was used to type HLA-A -B, -Cw, and -DR antigens. The frequenci es of these antigens in relation to lymphocytotoxic anti-HLA-A-B-Cw-DR antibodies and two environmental factors (Yersinia enterocolitica and Coxsackie B virus) were determined. The frequencies of HLA-B15, -B21 and DR3 antigens were increased, whereas HLA-DRS antigen was decreased in GD patients. A significant association between HLA-DR3 antigen and lymphocytotoxic antibodies was observed, i. e., IgGs from GD patients were cytotoxic to HLA-DR3+ normal B cells. Following absorption with Yersinia enterocolitica or Coxsackie-B-virus, only Coxsackie-B virus c ompletely inhibited the lymphocytotoxic reactions against HLA-DR3(+) B cells. Besides confirming the association of HLA-DR3 with GD, this st udy also suggests the role of Coxsackie-reative HLA-DR3 antibodies as contributing factors to the pathogenesis of the disease.