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Abstract Number: 1236

IgG4 Immunostaining Is Common but Not Specific in Orbitbal Inflammatory Diseases

James T. Rosenbaum1,2, Amanda Wong3, Patrick Stauffer3, Megan Troxell4, Donald Houghton5, Dongseok Choi6, Christine Harrington7, David Wilson8, Hans Grossniklaus9, Roger Dailey3, John Ng3, Eric Steele3, Patrick Yeatts10, Peter Dolman11, Valerie White11, Craig Czyz12, Jill Foster12, Deepak Edward13, Hind Alkatan13, Don Kikkawa14, Bobby Korn15, Dinesh Selva16, Gerald Harris17, Michael Kazim18, Payal Patel18 and Stephen R. Planck19, 1OHSU, Portland, OR, 2Arthritis and Rheumatic diseases, Oregon Health and Science University, Portland, OR, 3Oregon Health & Science University, Portland, OR, 4Pathology, Oregon Health and Science University, Portland, OR, 5Pathology, Oregon Health & Science University, Portland, OR, 6Casey Eye Institute, Oregon Health and Science University, Portland, OR, 7Integrated Genomics, Oregon Health & Science University, Portland, OR, 8Casey Eye Institute/Ophthalmology, Oregon Health & Science University, Portland, OR, 9Ophthalmology, Emory University, Atlanta, GA, 10Ophthalmology, Wake Forest University, Winston-Salem, NC, 11University of British Columbia, Vancouver, BC, Canada, 12Ohio State Univeristy, Columbus, OH, 13King Khaled Eye Hospital, Riyadh, Saudi Arabia, 14Ophthalmology, University of California, San Diego, San Diego, CA, 15University of California, San Diego, San Diego, CA, 16Royal Adelaide Hospital, Adelaide, Australia, 17Medical College of Wisconsin, Milwaukee, WI, 18Columbia University, New York City, NY, 19Casey Eye Inst/Ophthalmology, Oregon Health & Science University, Portland, OR

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: IgG4 Related Disease, sarcoidosis and vasculitis, Sjogren's syndrome, Wegener's granulomatosis

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Session Information

Title: Miscellaneous Rheumatic and Inflammatory Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose: 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 109 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 27 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and anterior orbit adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix microarrays.

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. Subjects with NSOI and IgG4 staining did not have multisystem disease. 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 and do not consistently indicate a multisystem disease. 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.


Disclosure:

J. T. Rosenbaum,

Genentech and Biogen IDEC Inc.,

2;

A. Wong,
None;

P. Stauffer,
None;

M. Troxell,
None;

D. Houghton,
None;

D. Choi,
None;

C. Harrington,
None;

D. Wilson,
None;

H. Grossniklaus,
None;

R. Dailey,
None;

J. Ng,
None;

E. Steele,
None;

P. Yeatts,
None;

P. Dolman,
None;

V. White,
None;

C. Czyz,
None;

J. Foster,
None;

D. Edward,
None;

H. Alkatan,
None;

D. Kikkawa,
None;

B. Korn,
None;

D. Selva,
None;

G. Harris,
None;

M. Kazim,
None;

P. Patel,
None;

S. R. Planck,
None.

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