Autoantibodies to the Thyrotropin Receptor

Abstract
I. Introduction THE DISCOVERY in 1956 of thyroid-stimulating activity quite distinct from TSH in the serum of patients with hyperthyroid Graves' disease was followed by extensive investigations which established that this substance (originally termed long acting thyroid stimulator or LATS) was a thyroid-stimulating autoantibody which mimicked most if not all the effects of TSH (for reviews see Ref. 1–3). It was clearly possible, therefore, that TSH and the autoantibodies stimulated thyroid function by interacting with the same cell surface receptor. Evidence for this concept was first provided by studies of the effects of Graves' immunoglobulin G (IgG) on 125I-labeled TSH binding to its receptor in thyroid membranes. These investigations indicated that TSH binding was readily inhibited in a dose-dependent manner by Graves' IgGs and suggested that the IgGs contained antibodies to the TSH receptor (4–6). Many subsequent investigations showed beyond reasonable doubt that this was indeed the case. The current review considers some of the more recent developments in this field with particular emphasis on the measurement of TSH receptor antibodies (TRAb) and their sites of action and synthesis.