The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment. PLoS One 2015;10(9):e0137654
Date
09/16/2015Pubmed ID
26371757Pubmed Central ID
PMC4570801DOI
10.1371/journal.pone.0137654Scopus ID
2-s2.0-84945588436 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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.
Author List
Rosenbaum JT, Choi D, Wong A, Wilson DJ, Grossniklaus HE, Harrington CA, Dailey RA, Ng JD, Steele EA, Czyz CN, Foster JA, Tse D, Alabiad C, Dubovy S, Parekh PK, Harris GJ, Kazim M, Patel PJ, White VA, Dolman PJ, Edward DP, Alkatan HM, Al Hussain H, Selva D, Yeatts RP, Korn BS, Kikkawa DO, Stauffer P, Planck SRAuthor
Gerald J. Harris MD Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultCase-Control Studies
Eye Diseases
Female
Gene Expression Profiling
Humans
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Orbit
Thyroid Diseases
