EVIDENCE FOR A RETROVIRAL TRIGGER IN GRAVES-DISEASE

An apparently high frequency of Graves' disease encountered in New Orl eans, Louisiana, prompted an investigation for a possible infectious a gent that might be triggering the disease in genetically susceptible i ndividuals. We studied 40 patients with Graves' disease, and compared them to the following groups of controls; age and gender matched healt hy subjects; patients with multinodular goiter (non-autoimmune thyroid controls); patients with chronic lymphocytic thyroiditis (autoimmune thyroid disease controls) and additional organ or tissue specific auto immune controls exclusive of thyroid autoimmunity, including patients with Type I diabetes and other endocrine autoimmune complex disorders. Serum antibodies against a prototypic strain of a human intracisterna l A-type retroviral particle type 1 (HIAP-1) were detected by a sensit ive and specific immunoblotting assay. In 87.5% (35/40) of the Graves' disease patients there was a positive reaction against several HIAP-1 -associated proteins, predominantly 97 Kd and 80 Kd, with only 5 showi ng no reactivity to any. In contrast, 2% (2/105) of sera from normal c ontrols showed positive reactivity. Furthermore, only 10% (1/10) of se ra from multinodular goiter control patients and 10% (1/10) of Hashimo to's patients showed reactivity (p < 0.0005). Sera from 3 of 20 (15%) of Type I diabetic patients none of whom had Graves' disease, showed r eactivity but there was no reactivity in 9 other patients with one or more of the endocrine autoimmune complex disorders, including Addison' s disease, vitiligo, myasthenia gravis and pernicious anemia. In addit ion we studied two individuals with Graves' disease from each of two f amilies residing outside Louisiana, all of whom were positive for thes e antibodies. Taken as a whole, these findings strongly suggest that i n genetically susceptible individuals exposure to retroviral antigens may precipitate the autoimmune responses leading to Graves' disease.