Thyroid-stimulating autoantibody production in vitro

Abstract

GRAVES' disease is an autoimmune disorder in which hyperthyroidism is associated with the presence of thyroid-stimulating autoantibodies¹. Recent work suggests that these antibodies, collectively termed TSAb, are antibodies to the thyrotrophin (TSH) receptor which stimulate the thyroid by binding to the receptor and activating adenylate cyclase^1–5. Synthesis of the autoantibody in vivo may result from defects in both the thyroid and the immune system. In the case of the thyroid, this may be an aberration in the synthesis or shedding of plasma membrane components related to the TSH receptor. In the case of the immune system, a current view is that autoantibody formation is the result of a suppressor T cell defect⁶. An in vitro model of TSAb synthesis would permit an analysis of the role of the thyroid and the immune system in the events leading to thyroid-stimulating antibody production. Attempts have been made to study TSAb production in short-term cultures of peripheral blood lymphocytes from Graves' patients. These studies, however, did not use optimal conditions for immunoglobulin production and the levels of TSAb reported were close to the limits of detectability of the imprecise assay methods used^7–11. In the study described here we have used the optimal conditions for culturing lymphocytes provided by Marbrook flasks¹² in conjunction with two new sensitive and precise methods for detecting TSAb—the radio-receptor¹³ and cytochemical assays^14,15. With this system we have readily been able to detect TSAb production in cultures of Graves' lymphocytes.