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George J. Kahaly, The Thyrocyte-Fibrocyte Link: Closing the Loop in the Pathogenesis of Graves’ Disease?, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 1, 1 January 2010, Pages 62–65, https://doi.org/10.1210/jc.2009-2405
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Graves’ disease (GD) is an antibody-driven autoimmune process affecting the thyroid gland and extrathyroidal target tissues in roughly 90% of the cases (1). Generation of activating autoantibodies against the TSH receptor (TSHR) leads to excessive thyroid hormone synthesis uniquely in GD (2). However, the mechanisms underlying extrathyroidal tissue inflammation and remodeling remain uncertain, as does their relationship with the processes occurring in the thyroid. Manifestations of GD include thyrotoxicosis and several extrathyroidal signs including Graves’ orbitopathy (GO), dermopathy, and acropachy (3). GO and dermopathy are connective tissue manifestations of GD. Tissue remodeling is a prominent feature of both and is apparently controlled by adaptive T cells. Lymphocytes and other bone marrow-derived cells recruited into the orbit appear to be the major effectors of autoagressive tissue destruction in GO. The most likely sequence of events is that T cells infiltrate the orbital and dermal connective tissue and respond to a depot of orbital/dermal autoantigens that display an identical structure to have epitopes that cross-react with a thyroid autoantigen (1–3). Orbital fibroblasts comprise a heterogeneous population of cells possessing divergent phenotypes and potential for differentiation. They represent a bimodal population of cells with regard to the surface display of the glycoprotein, Thy1. Moreover, they exhibit attributes differing from their nonorbital counterparts that may underlie anatomic-selective involvement of the orbit in GD (4). Thus, orbital fibroblasts exhibit a unique phenotype, including exaggerated responses to proinflammatory cytokines.
