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Type: Journal article
Title: The role of the immune response in the pathogenesis of thyroid eye disease: a reassessment
Author: Rosenbaum, J.
Choi, D.
Wong, A.
Wilson, D.
Grossniklaus, H.
Harrington, C.
Dailey, R.
Ng, J.
Steele, E.
Czyz, C.
Foster, J.
Tse, D.
Alabiad, C.
Dubovy, S.
Parekh, P.
Harris, G.
Kazim, M.
Patel, P.
White, V.
Dolman, P.
et al.
Citation: PLoS One, 2015; 10(9):e0137654-1-e0137654-12
Publisher: Public Library of Science
Issue Date: 2015
ISSN: 1932-6203
Editor: Pietropaolo, M.
Statement of
James T. Rosenbaum ... Dinesh Selva ... et al.
Abstract: BACKGROUND: Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray. METHODS: An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets. RESULTS: Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED. CONCLUSION: This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.
Keywords: Orbit
Eye Diseases
Thyroid Diseases
Oligonucleotide Array Sequence Analysis
Case-Control Studies
Gene Expression Profiling
Middle Aged
Rights: © 2015 Rosenbaum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
DOI: 10.1371/journal.pone.0137654
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