INHIBITION OF FUNCTIONAL AND IMMUNOLOGICAL RESPONSES TO THYROID-STIMULATING ANTIBODIES FROM PATIENTS WITH GRAVES-DISEASE BY BLOCKADE OF THETHYROTROPIN RECEPTOR
R. Hoermann et al., INHIBITION OF FUNCTIONAL AND IMMUNOLOGICAL RESPONSES TO THYROID-STIMULATING ANTIBODIES FROM PATIENTS WITH GRAVES-DISEASE BY BLOCKADE OF THETHYROTROPIN RECEPTOR, Thyroid, 3(4), 1993, pp. 273-278
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.