title: The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Medicine, Oregon Health & Science University, Portland, Oregon, United States of America; Devers Eye Institute, Legacy Health Systems, Portland, Oregon, United States of America.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Wong
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Harrington
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dailey
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Ng
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Steele
authors.affiliation: Division of Ophthalmology, Ohio University, Athens, Ohio, United States of America.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Czyz
authors.affiliation: Department of Ophthalmology, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Foster
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Tse
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, United States of America.
authors.forename: Chris
authors.initials: C
authors.lastname: Alabiad
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, United States of America.
authors.forename: Sander
authors.initials: S
authors.lastname: Dubovy
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, United States of America.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Parekh
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Harris
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Kazim
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States of America.
authors.forename: Payal J
authors.initials: PJ
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: White
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dolman
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Edward
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hind M
authors.initials: HM
authors.lastname: Alkatan
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hailah
authors.initials: H
authors.lastname: Al Hussain
authors.affiliation: Ophthalmology Network, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Selva
authors.affiliation: Department of Ophthalmology, Wake Forrest University, Winston-Salem, North Carolina, United States of America.
authors.forename: R Patrick
authors.initials: RP
authors.lastname: Yeatts
authors.affiliation: Department of Ophthalmology, University of California, San Diego, California, United States of America.
authors.forename: Bobby S
authors.initials: BS
authors.lastname: Korn
authors.affiliation: Department of Ophthalmology, University of California, San Diego, California, United States of America.
authors.forename: Don O
authors.initials: DO
authors.lastname: Kikkawa
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stauffer
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Medicine, Oregon Health & Science University, Portland, Oregon, United States of America; Devers Eye Institute, Legacy Health Systems, Portland, Oregon, United States of America.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005128:Eye Diseases / Q000150:complications* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D009915:Orbit / Q000473:pathology; D013959:Thyroid Diseases / Q000150:complications*