Lgg4 immunostaining and its implications in orbital inflammatory disease

Amanda J. Wong, Stephen R. Planck, Dongseok Choi, Christina A. Harrington, Megan L. Troxell, Donald C. Houghton, Patrick Stauffer, David J. Wilson, Hans E. Grossniklaus, Roger A. Dailey, John D. Ng, Eric A. Steele, Gerald J. Harris, Craig Czyz, Jill A. Foster, Valerie A. White, Peter J. Dolman, Michael Kazim, Payai J. Patel, Deepak P. EdwardHind Al Katan, Hailah Al Hussain, Dinesh Selva, R. Patrick Yeatts, Bobby S. Korn, Don O. Kikkawa, James T. Rosenbaum

Research output: Contribution to journalArticle

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Abstract

Methods: We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for lgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays.

Results: None of the healthy controls or subjects with TED had substantial lgG4 staining. Among the 63 others, the prevalence of significant lgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. lgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of lgG4+ cells correlated with inflammation in the lacrimal gland based on histology. lgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this.

Conclusion: lgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 lgG4+ cells/high powered field, lgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.

Objective: lgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of lgG4 immunostaining, we analyzed gene expression and the prevalence of lgG4immunostaining among subjects with orbital inflammatory diseases.

Original languageEnglish (US)
Article numbere10984
JournalPLoS One
Volume9
Issue number10
DOIs
StatePublished - Oct 10 2014

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Orbital Diseases
lacrimal apparatus
Lacrimal Apparatus
Granulomatosis with Polyangiitis
Sarcoidosis
Staining and Labeling
eye diseases
Tissue
Eye Diseases
inflammation
plasma cells
Thyroid Diseases
Plasma Cells
Inflammation
histology
biopsy
Histology
Biopsy
Gene Expression
gene expression

ASJC Scopus subject areas

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

Cite this

Lgg4 immunostaining and its implications in orbital inflammatory disease. / Wong, Amanda J.; Planck, Stephen R.; Choi, Dongseok; Harrington, Christina A.; Troxell, Megan L.; Houghton, Donald C.; Stauffer, Patrick; Wilson, David J.; Grossniklaus, Hans E.; Dailey, Roger A.; Ng, John D.; Steele, Eric A.; Harris, Gerald J.; Czyz, Craig; Foster, Jill A.; White, Valerie A.; Dolman, Peter J.; Kazim, Michael; Patel, Payai J.; Edward, Deepak P.; Katan, Hind Al; Hussain, Hailah Al; Selva, Dinesh; Yeatts, R. Patrick; Korn, Bobby S.; Kikkawa, Don O.; Rosenbaum, James T.

In: PLoS One, Vol. 9, No. 10, e10984, 10.10.2014.

Research output: Contribution to journalArticle

Wong, AJ, Planck, SR, Choi, D, Harrington, CA, Troxell, ML, Houghton, DC, Stauffer, P, Wilson, DJ, Grossniklaus, HE, Dailey, RA, Ng, JD, Steele, EA, Harris, GJ, Czyz, C, Foster, JA, White, VA, Dolman, PJ, Kazim, M, Patel, PJ, Edward, DP, Katan, HA, Hussain, HA, Selva, D, Yeatts, RP, Korn, BS, Kikkawa, DO & Rosenbaum, JT 2014, 'Lgg4 immunostaining and its implications in orbital inflammatory disease', PLoS One, vol. 9, no. 10, e10984. https://doi.org/10.1371/journal.pone.0109847
Wong, Amanda J. ; Planck, Stephen R. ; Choi, Dongseok ; Harrington, Christina A. ; Troxell, Megan L. ; Houghton, Donald C. ; Stauffer, Patrick ; Wilson, David J. ; Grossniklaus, Hans E. ; Dailey, Roger A. ; Ng, John D. ; Steele, Eric A. ; Harris, Gerald J. ; Czyz, Craig ; Foster, Jill A. ; White, Valerie A. ; Dolman, Peter J. ; Kazim, Michael ; Patel, Payai J. ; Edward, Deepak P. ; Katan, Hind Al ; Hussain, Hailah Al ; Selva, Dinesh ; Yeatts, R. Patrick ; Korn, Bobby S. ; Kikkawa, Don O. ; Rosenbaum, James T. / Lgg4 immunostaining and its implications in orbital inflammatory disease. In: PLoS One. 2014 ; Vol. 9, No. 10.
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abstract = "Methods: We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for lgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays.Results: None of the healthy controls or subjects with TED had substantial lgG4 staining. Among the 63 others, the prevalence of significant lgG4-immunostaining ranged from 11 to 39{\%} depending on the definition for significant. lgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of lgG4+ cells correlated with inflammation in the lacrimal gland based on histology. lgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this.Conclusion: lgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 lgG4+ cells/high powered field, lgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.Objective: lgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of lgG4 immunostaining, we analyzed gene expression and the prevalence of lgG4immunostaining among subjects with orbital inflammatory diseases.",
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T1 - Lgg4 immunostaining and its implications in orbital inflammatory disease

AU - Wong, Amanda J.

AU - Planck, Stephen R.

AU - Choi, Dongseok

AU - Harrington, Christina A.

AU - Troxell, Megan L.

AU - Houghton, Donald C.

AU - Stauffer, Patrick

AU - Wilson, David J.

AU - Grossniklaus, Hans E.

AU - Dailey, Roger A.

AU - Ng, John D.

AU - Steele, Eric A.

AU - Harris, Gerald J.

AU - Czyz, Craig

AU - Foster, Jill A.

AU - White, Valerie A.

AU - Dolman, Peter J.

AU - Kazim, Michael

AU - Patel, Payai J.

AU - Edward, Deepak P.

AU - Katan, Hind Al

AU - Hussain, Hailah Al

AU - Selva, Dinesh

AU - Yeatts, R. Patrick

AU - Korn, Bobby S.

AU - Kikkawa, Don O.

AU - Rosenbaum, James T.

PY - 2014/10/10

Y1 - 2014/10/10

N2 - Methods: We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for lgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays.Results: None of the healthy controls or subjects with TED had substantial lgG4 staining. Among the 63 others, the prevalence of significant lgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. lgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of lgG4+ cells correlated with inflammation in the lacrimal gland based on histology. lgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this.Conclusion: lgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 lgG4+ cells/high powered field, lgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.Objective: lgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of lgG4 immunostaining, we analyzed gene expression and the prevalence of lgG4immunostaining among subjects with orbital inflammatory diseases.

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