INHIBITION OF FUNCTIONAL AND IMMUNOLOGICAL RESPONSES TO THYROID-STIMULATING ANTIBODIES FROM PATIENTS WITH GRAVES-DISEASE BY BLOCKADE OF THETHYROTROPIN RECEPTOR

Thyrotropin (TSH) receptor is the main autoantigen and the target of t hyroid-stimulating antibodies in Graves disease. In the present studie s, in order to shed further light on the role of TSH receptor in thyro id autoimmune disease, we investigated the effects of TSH receptor blo ckade on functional and immunological responses to thyroid stimulation by Graves' immunoglobulins in the nude mouse bearing human thyroid tr ansplants. Injecting the nude mice with purified Graves' immunoglobuli ns G resulted in a dose-dependent stimulation of thyroid hormone produ ction, an inducement of cellular hypertrophy of transplant thyrocytes, and an expression of the HLA-DR antigen by up to 75% of the transplan t thyroid follicular cells. Treatment of the animals with the TSH rece ptor antagonist asialoagalacto-hCG was able to inhibit the stimulation by Graves' immunoglobulins G of thyroxine production, cellular hypert rophy of transplant thyrocytes, and HLA-DR expression by thyroid folli cular cells in the human transplants. The present data provide direct evidence for an involvement of the human TSH receptor in mediating bot h the functional disturbance (hyperthyroidism) and the immunological d isorder in Graves' disease and add further support to the concept of u sing TSH receptor antagonists in the management of the disease.