The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment

• Type of Material: Article
• Authors: James T. Rosenbaum, Oregon Health & Science University; Dongseok Choi, Oregon Health & Science University; Amanda Wong, Oregon Health & Science University; David J Wilson, Oregon Health & Science University; Hans Grossniklaus, Emory University; Christina A. Harrington, Oregon Health & Science University; Roger A. Dailey, Oregon Health & Science University; John D. Ng, Oregon Health & Science University; Eric A. Steele, Oregon Health & Science University; Craig N. Czyz, Ohio University; Jill A. Foster, The Ohio State University; David Tse, University of Miami; Chris Alabiad, University of Miami; Sander Dubovy, Oregon Health & Science University; Prashant K. Parekh, University of Miami; Gerald J. Harris, Medical College of Wisconsin; Michael Kazim, Columbia University; Payal J. Patel, Columbia University; Valerie A. White, University of British Columbia; Peter J. Dolman, University of British Columbia; Deepak P. Edward, King Khaled Eye Specialist Hospital; Hind M. Alkatan, King Khaled Eye Specialist Hospital; Hailah al Hussain, King Khaled Eye Specialist Hospital; Dinesh Selva, Royal Adelaide Hospital; R. Patrick Yeatts, Wake Forrest University; Bobby S. Korn, University of California; Don O. Kikkawa, University of California; Patrick Stauffer, Oregon Health & Science University; Stephen R. Planck, Oregon Health & Science University
• Language: English
• Date: 2015-09-15
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Rosenbaum et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0137654
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 10
• Issue: 9
• Start Page: e0137654
• End Page: e0137654
• Grant/Funding Information: Research to Prevent Blindness (www.rpbusa.org) (Casey Eye Institute, OHSU), the Stan and Madelle Rosenfeld Family Trust (JTR), the William and Mary Bauman Foundation (JTR), the MAS Family Foundation (JTR).; This research was supported by funding from National Institutes of Health USA Grants (www.nih.gov), EY020249 (JTR), EY010572 (JTR) and RR024140 (E.S.Orwoll)
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Opthamology

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.