title: IgG4 immunostaining and its implications in orbital inflammatory disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Wong
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Medicine, Oregon Health & Science University, Portland, Oregon, United States of America; Devers Eye Institute, Legacy Health Systems, Portland, Oregon, United States of America.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Harrington
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Troxell
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Houghton
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stauffer
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dailey
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Ng
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Steele
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Harris
authors.affiliation: Division of Ophthalmology, Ohio University, Columbus, Ohio, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Czyz
authors.affiliation: Department of Ophthalmology, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Foster
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: White
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dolman
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Kazim
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, United States of America.
authors.forename: Payal J
authors.initials: PJ
authors.lastname: Patel
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Edward
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hind
authors.initials: H
authors.lastname: al Katan
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hailah
authors.initials: H
authors.lastname: al Hussain
authors.affiliation: Ophthalmology Network, Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Selva
authors.affiliation: Department of Ophthalmology, Wake Forrest University, Winston-Salem, North Carolina, United States of America.
authors.forename: R Patrick
authors.initials: RP
authors.lastname: Yeatts
authors.affiliation: Department of Ophthalmology, University of California San Diego, San Diego, California, United States of America.
authors.forename: Bobby S
authors.initials: BS
authors.lastname: Korn
authors.affiliation: Department of Ophthalmology, University of California San Diego, San Diego, California, United States of America.
authors.forename: Don O
authors.initials: DO
authors.lastname: Kikkawa
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America; Department of Medicine, Oregon Health & Science University, Portland, Oregon, United States of America; Devers Eye Institute, Legacy Health Systems, Portland, Oregon, United States of America.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005128:Eye Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods*; D007765:Lacrimal Apparatus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009915:Orbit / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D007074:Immunoglobulin G