IgG4 immunostaining and its implications in orbital inflammatory disease

• Published in: PloS one Vol. 9; no. 10; p. e109847
• Main Authors: 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, Payal J, Edward, Deepak P, al Katan, Hind, al Hussain, Hailah, Selva, Dinesh, Yeatts, R Patrick, Korn, Bobby S, Kikkawa, Don O, Rosenbaum, James T
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-10-2014; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Adult; Aged; Analysis; Annotations; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmune Diseases - pathology; Biology and Life Sciences; Consortia; Eye diseases; Eye Diseases - immunology; Eye Diseases - metabolism; Eye Diseases - pathology; Female; Gene expression; Granulomatosis; Health care; Histology; Hospitals; Humans; Immunoglobulin G; Immunoglobulin G - metabolism; Immunoglobulins; Immunohistochemistry - methods; Inflammation; Inflammatory diseases; Lacrimal Apparatus - immunology; Lacrimal Apparatus - metabolism; Lacrimal Apparatus - pathology; Lacrimal gland and Nasolacrimal duct; Lymphocytes B; Male; Medicine and Health Sciences; Middle Aged; Orbit - immunology; Orbit - metabolism; Orbit - pathology; Pancreatitis; Physicians; Plasma cells; Preventive medicine; Rheumatoid arthritis; Ribonucleic acid; RNA; Sarcoidosis; Science; Staining; Studies; Systemic diseases; Thyroid; Tissues; Vein & artery diseases; Saudi Arabia; Oregon; Canada; New York; United States > US; Ohio; California; Riyadh Saudi Arabia; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109847

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.
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.
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.
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.