Role of anti‐receptor autoantibodies in tissue remodeling.

Abstract

The ocular manifestation of Graves’ disease (GD), known as thyroid‐associated ophthalmopathy (TAO), is an autoimmune process where the tissues of the upper face and orbits become inflamed and undergo remodeling. TAO remains a disfiguring and potentially blinding disease for which no medical treatments has yet to be approved by the FDA. Initiating TAO are thought to be immune responses to autoantigen(s) shared by the thyroid and orbit. The two leading candidate autoantigens in this disease are the thyrotropin receptor (TSHR) and insulin‐like growth factor receptor (IGF‐IR). Autoantibodies against TSHR drive thyroid over‐production of thyroid hormones in GD while anti‐IGF‐IR antibodies can be detected in patients with GD and TAO. Anti‐IGF‐IR antibodies have yet to be characterized and their role in GD remains controversial. Here I will discuss the current evidence supporting autoantibodies as driving the development of TAO and the downstream consequences of cell‐surface signaling they initiate. Further, identification of these antibody‐dependent processes has led to the development of promising therapeutic candidates for TAO, a vexing and poorly treated disease.