Faculty Collaboration Database

Gene Expression Profiling and Heterogeneity of Nonspecific Orbital Inflammation Affecting the Lacrimal Gland. JAMA Ophthalmol 2017 Nov 01;135(11):1156-1162

Date

10/05/2017

Pubmed ID

28975236

Pubmed Central ID

PMC6033262

DOI

10.1001/jamaophthalmol.2017.3458

Scopus ID

2-s2.0-85034624407 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

IMPORTANCE: Although a variety of well-characterized diseases, such as sarcoidosis and granulomatosis with polyangiitis, affect the lacrimal gland, many patients with dacryoadenitis are diagnosed as having nonspecific orbital inflammation (NSOI) on the basis of histology and systemic disease evaluation. The ability to further classify the disease in these patients should facilitate selection of effective therapies.

OBJECTIVE: To test the a priori hypothesis that gene expression profiles would complement clinical and histopathologic evaluations in identifying well-characterized diseases and in subdividing NSOI into clinically relevant groups.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, gene expression levels in biopsy specimens of inflamed and control lacrimal glands were measured with microarrays. Stained sections of the same biopsy specimens were used for evaluation of histopathology. Tissue samples of patients were obtained from oculoplastic surgeons at 7 international centers representing 4 countries (United States, Saudi Arabia, Canada, and Taiwan). Gene expression analysis was done at Oregon Health & Science University. Participants were 48 patients, including 3 with granulomatosis with polyangiitis, 28 with NSOI, 7 with sarcoidosis, 4 with thyroid eye disease, and 6 healthy controls. The study dates were March 2012 to April 2017.

MAIN OUTCOMES AND MEASURES: The primary outcome was subdivision of biopsy specimens based on gene expression of a published list of approximately 40 differentially expressed transcripts in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis. Stained sections were evaluated for inflammation (none, mild, moderate, or marked), granulomas, nodules, or fibrosis by 2 independent ocular pathologists masked to the clinical diagnosis.

RESULTS: Among 48 patients (mean [SD] age, 41.6 [19.0] years; 32 [67%] female), the mclust algorithm segregated the biopsy specimens into 4 subsets, with the differences illustrated by a heat map and multidimensional scaling plots. Most of the sarcoidosis biopsy specimens were in subset 1, which had the highest granuloma score. Three NSOI biopsy specimens in subset 1 had no apparent granulomas. Thirty-two percent (9 of 28) of the NSOI biopsy specimens could not be distinguished from biopsy specimens of healthy controls in subset 4, while other examples of NSOI tended to group with gene expression resembling granulomatosis with polyangiitis or thyroid eye disease. The 4 subsets could also be partially differentiated by their fibrosis, granulomas, and inflammation pathology scores but not their lymphoid nodule scores.

CONCLUSIONS AND RELEVANCE: 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 NSOI cannot be distinguished from healthy controls.

Author List

Rosenbaum JT, Choi D, Harrington CA, Wilson DJ, Grossniklaus HE, Sibley CH, Salek SS, Ng JD, Dailey RA, Steele EA, Hayek B, Craven CM, Edward DP, Maktabi AMY, Al Hussain H, White VA, Dolman PJ, Czyz CN, Foster JA, Harris GJ, Bee YS, Tse DT, Alabiad CR, Dubovy SR, Kazim M, Selva D, Yeatts RP, Korn BS, Kikkawa DO, Silkiss RZ, Sivak-Callcott JA, Stauffer P, Planck SR

Author

Gerald J. Harris MD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Biopsy
Female
Gene Expression Profiling
Gene Expression Regulation
Genetic Markers
Humans
Lacrimal Apparatus
Lacrimal Apparatus Diseases
Male
Orbital Pseudotumor
RNA
Retrospective Studies
Tissue Array Analysis