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Current insights into the pathogenesis of Graves' orbitopathy

Eckstein, A. K., Johnson, K. T. M., Thanos, M., Esser, J. and Ludgate, Marian Elizabeth 2009. Current insights into the pathogenesis of Graves' orbitopathy. Hormone and Metabolic Research 41 (6) , pp. 456-464. 10.1055/s-0029-1220935

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Abstract

Graves' orbitopathy (GO) is part of an autoimmune disease constellation comprising hyperthyroidism, orbitopathy, pretibial myxedema, and acropachy. Signs and symptoms of GO occur due to inflammation of the orbital connective tissue, inflammation and fibrosis of the extraocular muscles, and adipogenesis. Stimulatory TSH receptor (TSHR) antibodies (TRAb) cause hyperthyroidism, but pathogenetic mechanisms in the orbit are less clear. The TSHR is one of the favoured candidate antigens; others such as the IGF1R might also play a role. Compared with other anatomical locations, orbital fibroblasts are extremely reactive to inflammatory stimuli, especially via CD40 activation. Orbital fibroblasts also differentiate into adipocytes, in response to the prevailing inflammatory cytokine milieu. Consequently TSHR gene expression increases together with expression of adipogenesis related genes. The same genes that confer susceptibility to Graves' disease (GD), both thyroid specific and immunoregulatory, also influence GO, although an increasing number of candidate genes with higher impact on orbitopathy are being identified. Smoking is the only environmental factor known to increase the likelihood and severity of GO developing in GD patients. A robust animal model of GO would facilitate the evaluation of new treatments. To date most models have centered on provoking autoimmune responses to the TSHR, but other antigens, alone or in combination with this receptor, hopefully will succeed in inducing the full spectrum of GD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: Graves' orbitopathy, environmental factors, genetic susceptibility, orbital autoantigens, orbital fibroblast, adipogenesis
Publisher: Georg Thieme Verlag
ISSN: 0018-5043
Last Modified: 04 Jun 2017 03:11
URI: http://orca.cf.ac.uk/id/eprint/17872

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