The role of the immune response in the pathogenesis of thyroid eye disease: A reassessment

James (Jim) Rosenbaum, Dongseok Choi, Amanda Wong, David Wilson, Hans E. Grossniklaus, Christina (Chris) Harrington, Roger Dailey, John Ng, Eric Steele, Craig N. Czyz, Jill A. Foster, David Tse, Chris Alabiad, Sander Dubovy, Prashant K. Parekh, Gerald J. Harris, Michael Kazim, Payal J. Patel, Valerie A. White, Peter J. DolmanDeepak P. Edward, Hind M. Alkatan, Hailah Al Hussain, Dinesh Selva, R. Patrick Yeatts, Bobby S. Korn, Don O. Kikkawa, Patrick Stauffer, Stephen Planck

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0137654
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 15 2015

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eye diseases
Eye Diseases
Thyroid Diseases
pathogenesis
Gene expression
immune response
Gene Expression
gene expression
Granulomatosis with Polyangiitis
Sarcoidosis
Orbital Diseases
inflammation
Tissue
Inflammation
Microarrays
Exophthalmos
Graves Disease
surgeons
chemokines
Principal Component Analysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The role of the immune response in the pathogenesis of thyroid eye disease : A reassessment. / Rosenbaum, James (Jim); Choi, Dongseok; Wong, Amanda; Wilson, David; Grossniklaus, Hans E.; Harrington, Christina (Chris); Dailey, Roger; Ng, John; Steele, Eric; Czyz, Craig N.; Foster, Jill A.; Tse, David; Alabiad, Chris; Dubovy, Sander; Parekh, Prashant K.; Harris, Gerald J.; Kazim, Michael; Patel, Payal J.; White, Valerie A.; Dolman, Peter J.; Edward, Deepak P.; Alkatan, Hind M.; Al Hussain, Hailah; Selva, Dinesh; Yeatts, R. Patrick; Korn, Bobby S.; Kikkawa, Don O.; Stauffer, Patrick; Planck, Stephen.

In: PLoS One, Vol. 10, No. 9, e0137654, 15.09.2015.

Research output: Contribution to journalArticle

Rosenbaum, JJ, Choi, D, Wong, A, Wilson, D, Grossniklaus, HE, Harrington, CC, Dailey, R, Ng, J, Steele, E, 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, S 2015, 'The role of the immune response in the pathogenesis of thyroid eye disease: A reassessment', PLoS One, vol. 10, no. 9, e0137654. https://doi.org/10.1371/journal.pone.0137654
Rosenbaum, James (Jim) ; Choi, Dongseok ; Wong, Amanda ; Wilson, David ; Grossniklaus, Hans E. ; Harrington, Christina (Chris) ; Dailey, Roger ; Ng, John ; Steele, Eric ; Czyz, Craig N. ; Foster, Jill A. ; Tse, David ; Alabiad, Chris ; Dubovy, Sander ; Parekh, Prashant K. ; Harris, Gerald J. ; Kazim, Michael ; Patel, Payal J. ; White, Valerie A. ; Dolman, Peter J. ; Edward, Deepak P. ; Alkatan, Hind M. ; Al Hussain, Hailah ; Selva, Dinesh ; Yeatts, R. Patrick ; Korn, Bobby S. ; Kikkawa, Don O. ; Stauffer, Patrick ; Planck, Stephen. / The role of the immune response in the pathogenesis of thyroid eye disease : A reassessment. In: PLoS One. 2015 ; Vol. 10, No. 9.
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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.",
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T1 - The role of the immune response in the pathogenesis of thyroid eye disease

T2 - A reassessment

AU - Rosenbaum, James (Jim)

AU - Choi, Dongseok

AU - Wong, Amanda

AU - Wilson, David

AU - Grossniklaus, Hans E.

AU - Harrington, Christina (Chris)

AU - Dailey, Roger

AU - Ng, John

AU - Steele, Eric

AU - Czyz, Craig N.

AU - Foster, Jill A.

AU - Tse, David

AU - Alabiad, Chris

AU - Dubovy, Sander

AU - Parekh, Prashant K.

AU - Harris, Gerald J.

AU - Kazim, Michael

AU - Patel, Payal J.

AU - White, Valerie A.

AU - Dolman, Peter J.

AU - Edward, Deepak P.

AU - Alkatan, Hind M.

AU - Al Hussain, Hailah

AU - Selva, Dinesh

AU - Yeatts, R. Patrick

AU - Korn, Bobby S.

AU - Kikkawa, Don O.

AU - Stauffer, Patrick

AU - Planck, Stephen

PY - 2015/9/15

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N2 - 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.

AB - 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.

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