Nature 275, 314 - 315 (28 September 1978); doi:10.1038/275314a0

Evidence that the TSH receptor acts as a mitogenic antigen in Graves' disease

TUULIKKI MÄKINEN^*†, GUSTAV WÄGAR^‡, LEIF APTER^§, EEVA VON WILLEBRAND & FREDRIKA PEKONEN^¶

^†Endocrine Research Unit, University of Helsinki, Helsinki, Finland
^‡Mjölbolsta Hospital, Helsinki, Finland
^§IV Department of Medicine, Helsinki University Hospital, Helsinki, Finland
Maria Hospital, Helsinki, Finland
^¶Endocrine Research Unit, University of Helsinki, Helsinki, Finland
^*To whom correspondence should be addressed at the Endocrine Research Unit, University of Helsinki, POB 819, SF-00101 Helsinki 10, Finland.

GRAVES' DISEASE (GD) is an autoimmune disorder associated with the formation of thyroid antibodies, one class of which, thyroid-stimulating antibodies (TSAb), is thought to be involved in the pathogenesis¹⁻³. TSAb act similarly to thyrotropin (TSH) on the thyroid follicle cell through the mediation of adenylate cyclase⁴. The formation of TSAb is thought to be due to a change in the immune tolerance or to some alteration of the antigen, which has been suggested to be the TSH receptor². Some experimental evidence favours a defect in the immune surveillance, caused by decreased suppressor T-cell function^2,5. It has been reported that sensitised lymphocytes from patients with GD can produce TSAb in vitro after nonspecific stimulation^6,7 as well as after specific stimulation with thyroid homogenate⁸. We report here that the lymphocyte-stimulating effect of thyroid membranes is abolished if the thyroid membranes are preincubated with TSH. According to our hypothesis, this means that the TSH receptor is the mitogenic antigen.

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