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

28 Scopus citations

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

ASJC Scopus subject areas

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

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    Wong, A. J., Planck, S. R., Choi, D., Harrington, C. A., Troxell, M. L., Houghton, D. C., Stauffer, P., Wilson, D. J., Grossniklaus, H. E., Dailey, R. A., Ng, J. D., Steele, E. A., Harris, G. J., Czyz, C., Foster, J. A., White, V. A., Dolman, P. J., Kazim, M., Patel, P. J., ... Rosenbaum, J. T. (2014). Lgg4 immunostaining and its implications in orbital inflammatory disease. PloS one, 9(10), [e10984]. https://doi.org/10.1371/journal.pone.0109847