IgG4 immunostaining and its implications in orbital inflammatory disease. PLoS One 2014;9(10):e109847
Date
10/11/2014Pubmed ID
25303270Pubmed Central ID
PMC4193851DOI
10.1371/journal.pone.0109847Scopus ID
2-s2.0-84907841722 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
OBJECTIVE: IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases.
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 IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays.
RESULTS: None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 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 IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this.
CONCLUSION: IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.
Author List
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, al Katan H, al Hussain H, Selva D, Yeatts RP, Korn BS, Kikkawa DO, Rosenbaum JTAuthor
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
AdultAged
Autoimmune Diseases
Eye Diseases
Female
Humans
Immunoglobulin G
Immunohistochemistry
Lacrimal Apparatus
Male
Middle Aged
Orbit