Gene Expression Levels in Sarcoidosis Patients with Uveitis

Abstract

Purpose: The diagnosis of sarcoid uveitis remains challenging as intraocular tissues are not typically amenable to biopsy, which is the current gold standard for diagnosing this granulomatous disease. Recent studies have shown that specific genes are not only important in pulmonary sarcoidosis activity and progression, but also allow for the differentiation of pulmonary sarcoidosis from other inflammatory lung diseases. Our objective was to compare the expression levels for genes previously described to be discriminative of pulmonary sarcoidosis in patients with and without uveitis in the setting of pulmonary sarcoidosis. We hypothesized that patients with uveitis in the setting of pulmonary sarcoidosis would exhibit similar expression levels for genes implicated in sarcoid activity as well as genes discriminative for sarcoid.

Methods: We reviewed the gene expression levels for subjects with biopsy proven pulmonary sarcoidosis previously enrolled into a longitudinal study in which peripheral blood was drawn for gene expression levels. Expression levels had been previously assessed via quantitative PCR, being expressed as log₂ cycle threshold values relative to mean healthy control cycle threshold values. Patients were categorized as having uveitis (based on a health-assessment questionnaire) or not having uveitis. We performed random effects modeling for each candidate gene comparing patients with uveitis to those without uveitis and controlled for FEV1/FVC ratio. Bonferroni correction was also performed.

Results: Gene expression levels were available for 167 subjects and 12 of these subjects had uveitis.<br /> We found no significant difference in expression levels sarcoid-discriminative genes (p values > 0.05) between patients with uveitis and pulmonary sarcoidosis and sarcoid patients without uveitis. Additionally, there were no significant differences in expression levels between the two groups of patients for 45 other genes important in granulomatous inflammation.

Conclusions: The gene expression profile between pulmonary sarcoidosis patients with and without uveitis appears to be comparable. While no significant differences in gene expression levels between the two groups of patients was identified, we plan on further correlating changes of gene expression levels longitudinally with uveitis activity.