title: Pathogenesis of Graves' ophthalmopathy: the role of autoantibodies.
abstract: The clinical manifestations of Graves' ophthalmopathy (GO) stem from a combination of increased orbital fat and extraocular muscle volume within the orbital space. Fibroblasts residing within orbital tissues are thought to be targets of autoimmune attack in the disease. Thyrotropin receptor (TSHr) mRNA and functional protein have been demonstrated in orbital fibroblasts from both normal individuals and GO patients, with higher levels present in the latter. Autoantibodies directed against TSHr or the insulin-like growth factor-1 (IGF-1) receptor have been implicated in GO pathogenesis. Evidence from our laboratory suggests that monoclonal TSHr autoantibodies (TRAbs) are potent stimulators of adipogenesis in GO orbital cells. Therefore, it is possible that circulating TRAbs in Graves' patients both stimulate overproduction of thyroid hormones and increase orbital adipose tissue volume. Antibodies to the IGF-1 receptor appear to impact GO pathogenesis through recruitment and activation of T-cells and stimulation of hyaluronan production, processes that play key roles in the development of inflammation and increased orbital tissue swelling. Although originally thought to represent another causative agent, antibodies to extraocular muscles are now generally thought to be secondary to extraocular muscle inflammation and damage.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Teck Kim
authors.initials: TK
authors.lastname: Khoo
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Bahn
mesh_terms: D001323:Autoantibodies / Q000502:physiology*; D005347:Fibroblasts / Q000276:immunology; D049970:Graves Ophthalmopathy / Q000209:etiology* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D009801:Oculomotor Muscles / Q000503:physiopathology; D017526:Receptor, IGF Type 1 / Q000276:immunology; D011989:Receptors, Thyrotropin / Q000276:immunology
chemical_list: D001323:Autoantibodies; D011989:Receptors, Thyrotropin; D017526:Receptor, IGF Type 1