Bioassays for thyrotropin receptor autoantibodies

Abstract

Bioassays using animal models were essential tools in the discovery of thyrotropin and in enhancing our understanding of the physiology of the pituitary-thyroid axis. These same bioassays were also instrumental in the discovery of autoantibodies to the thyrotropin receptor (TSH-R-Ab) and in identifying their role in the pathophysiology of Graves' disease. The development of cell-based bioassays led to further advances in our knowledge of the functional activity of TSH-R-Ab and to the discovery that TSH-R-Ab can be either thyroid-stimulating or thyroid blocking, and that they occur in other types of autoimmune thyroid diseases (AITD) besides Graves' disease. More recently, TSH-R-Ab bioassays have been advanced from research tools to clinical laboratory tests. Whereas TSH-R-Ab can be measured with competitive-binding immunoassays, these assays do not provide information on the functional activity of TSH-R-Ab. Bioassays, in contrast, can differentiate between the stimulatory or blocking activity of TSH-R-Ab which provides clinically useful information that can inform the management of patients with AITD. The clinical use of TSH-R-Ab bioassays, however, has been limited to-date by their inherent complexity and long turn-around-time. Recent advances in biosensors have been applied to the development of TSH-R-Ab bioassays that are rapid and simple to perform. We now are entering an era in which bioassays for TSH-R-Ab can be measured routinely by virtually any clinical laboratory.

Keywords: CAMP; TSH receptor; bioassay; thyroid blocking antibodies; thyroid-stimulating antibodies.