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James T Rosenbaum, Dongseok Choi, Christina A. Harrington, David J Wilson, Hans E Grossniklaus, Patrick Stauffer, Stephen R Planck, Orbital Inflammatory Disease Consortium; Gene expression profiles of orbital adipose and lacrimal gland from subjects with sarcoidosis parallel some changes in blood. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5869.
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© ARVO (1962-2015); The Authors (2016-present)
Gene expression profiling has the potential to assist in the diagnosis and treatment selection for patients with orbital inflammation. We compared gene expression levels in orbital adipose and lacrimal gland of subjects with sarcoidosis with levels in uninflamed control tissues and then compared those profiles to one that we previously reported for blood.
Affymetrix U133 Plus 2 microarrays were used to determine relative mRNA levels in formalin-fixed, paraffin-embedded orbital biopsies of subjects with sarcoidosis (7 adipose, 5 lacrimal gland) and from subjects with no known orbital pathology (6 adipose, 6 lacrimal gland). Lists of probe sets with significantly increased or decreased signals in the sarcoidosis group were compared to similar list previously obtained from blood collected from subjects with sarcoidosis and healthy controls. The significance threshold was set at >1.5-fold difference with a false discovery rate of <0.05.
Significantly higher signals were obtained for 2457 probe sets (transcripts from ~1349 genes) for adipose and for 3077 probe sets (~2001 genes) for lacrimal gland from sarcoidosis subjects. Significantly lower signals were obtained for 4050 probe sets (~2769 genes) for adipose and 3320 probe sets (~2283 genes) for lacrimal gland from sarcoidosis subjects. After comparing lists of the differentially expressed transcripts for orbital adipose, lacrimal gland, and blood, we identified 92 probe sets (~69 genes) that had increased signals and found that these genes were enriched in binding sites for the transcription factors, IRF-1, IRF-2, and NFκB. Decreased signals were observed for 67 probe sets (~56 genes) in all three tissues from sarcoidosis patients.
Orbital adipose and lacrimal gland tissues from subjects with sarcoidosis can readily be distinguished from uninflamed control tissues. The list of genes elevated in all three tissues is consistent with previous reports from us and others that activation of a JAK/STAT pathway, such as by interferon signaling, is a common feature of sarcoidosis. These results support the idea that an algorithm based on gene expression in peripheral blood might assist in the diagnosis of sarcoidosis without a more invasive biopsy.
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