Читать книгу Graves' Orbitopathy - Группа авторов - Страница 50

It is widely accepted that GO is an autoimmune condition. A hypothesis on the pathogenesis of GO implies that the responsible autoantigens would be molecules expressed by thyroid cells that are also present in orbital tissues. TSH-R is regarded as the most suitable candidate. TSH-R is expressed and functionally active in orbital tissues [9, 12]. TSH, TSH-R-stimulating antibodies, and a monoclonal anti-TSH-R antibody are capable of upregulating the synthesis of hyaluronic acid and adipogenesis in orbital fibroblasts [13–15]. GO is almost invariably associated with circulating anti-TSH-R antibodies [7, 9, 12], and the severity and the activity of GO correlate with anti-TSH-R antibodies [16]. Finally, a recent animal model resembling to some extent GO was developed by genetic immunization of mice with TSH-R [17]. Recent studies have suggested that, by acting in concert with TSH-R, the insulin-like growth factor 1 receptor, which is also expressed by orbital fibroblasts, may be necessary for TSH-R-driven autoimmunity [18]. Another hypothesis involves thyroglobulin (Tg), the precursor of thyroid hormone, which implies that GO would follow deposition and accumulation of Tg following its release from the thyroid. Once in the orbit, Tg would trigger an autoimmune reaction thereby giving origin or contributing to the development and maintenance of GO [19]. As a matter of fact, Tg of thyroid origin (containing thyroid hormone residues) was found in orbital tissues of GO patients, but no Tg-anti-Tg immune complexes were detected, and no signs of GO have been reported in experimental models of autoimmune thyroiditis obtained in mice by immunization with Tg [19]. Thus, whether Tg is involved in the pathogenesis of GO remains to be established.