June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Gene Expression Profiling Reveals Heterogeneity of Nonspecific Inflammation Affecting the Lacrimal Gland
Author Affiliations & Notes
  • James T Rosenbaum
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
    Devers Eye Institute, Legacy Health System, Portland, Oregon, United States
  • Dongseok Choi
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
    School of Public Health, Oregon Health & Science University, Portland, Oregon, United States
  • Christina A Harrington
    Integrated Genomics Laboratory, Oregon Health & Science University, Portland, Oregon, United States
  • David J Wilson
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Hans E Grossniklaus
    Opthalmology, Emory University, Atlanta, Georgia, United States
  • Cailin H Sibley
    Medicine, Oregon Health & Science University, Portland, Oregon, United States
  • John D Ng
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Roger A Dailey
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Eric A Steele
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Stephen R Planck
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
    Devers Eye Institute, Legacy Health System, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   James Rosenbaum, Abbvie (C), Alcon Research Institute (F), Cavtherx (C), Eyevensys (C), Gilead (C), Mitotech (C), Portage (C), Regeneron (C), Santen (C), UpToDate (I); Dongseok Choi, None; Christina Harrington, None; David Wilson, None; Hans Grossniklaus, None; Cailin Sibley, None; John Ng, None; Roger Dailey, None; Eric Steele, None; Stephen Planck, None
  • Footnotes
    Support  NIH Grants EY020249, EY010572 & RR024140; Research To Prevent Blindness award to the CEI
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5617. doi:
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      James T Rosenbaum, Dongseok Choi, Christina A Harrington, David J Wilson, Hans E Grossniklaus, Cailin H Sibley, John D Ng, Roger A Dailey, Eric A Steele, Stephen R Planck; Gene Expression Profiling Reveals Heterogeneity of Nonspecific Inflammation Affecting the Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5617.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Although a variety of well characterized diseases such as sarcoidosis and granulomatosis with polyangiitis (GPA) affect the lacrimal gland, many patients with dacryoadenitis are labelled as having nonspecific inflammation (NSI) on the basis of histology and systemic disease evaluation. We previously published a common list of ~38 genes differentially expressed in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis based on 45 Affymetrix microarray probe sets. We tested the hypothesis that lacrimal inflammation could be subdivided on the basis of this core group of probe sets.

Methods : We obtained 49 lacrimal gland biopsies from 7 centers. The disease diagnoses were 4 thyroid eye disease, 8 sarcoidosis, 3 GPA, 28 NSI, and 6 healthy controls. We used Affymetrix Human U133 Plus 2 microarrays to determine gene expression levels in these tissues. After normalization, we applied the mclust clustering algorithm that segregated the samples into 4 subsets based on the signals from the core probe sets. H&E stained sections of each biopsy were evaluated for no, mild, moderate, or marked inflammation, granulomas, nodules, or fibrosis by two independent ocular pathologists.

Results : The heat map illustrates variation in gene expression profiles among the 4 subsets. Most of the sarcoid samples are in subset 1, which had the highest granuloma score. Interestingly, the 3 NSI samples in subset 1 had no apparent granulomas. 32% of the NSI samples could not be distinguished from samples of healthy controls, while other examples of NSI tended to group with gene expression resembling TED or GPA. The 4 subsets can be further differentiated by their fibrosis, inflammation, and nodule scores.

Conclusions : Gene expression profiling discloses clear heterogeneity among patients with lacrimal inflammatory disease. Comparison of the expression profiles suggests that a subset of patients with nonspecific dacryoadenitis might have a limited form of sarcoidosis while other patients with NSI cannot be distinguished from healthy controls.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

Heat map showing relative expression levels in 4 subsets based on the core probe sets. Yellow, high expression; blue, low expression; S, sarcoid; G, GPA; T, TED; N, NSI; C, control

Heat map showing relative expression levels in 4 subsets based on the core probe sets. Yellow, high expression; blue, low expression; S, sarcoid; G, GPA; T, TED; N, NSI; C, control

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