MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjögren's syndrome

Abstract

Objective MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjögren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction. Methods MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA. MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA. Results MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes. Conclusion Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers.

Human and Viral microRNA Expression in Sjögren Syndrome

“…This finding is in accordance with a previous study that identified many of the same viral microRNA unregulated in the salivary glands of pSS 17 .…”

Decreased microRNA-181a and -16 expression levels in the labial salivary glands of Sj�gren syndrome patients

“…However, only a limited number of studies have focused on understanding the miRNA function in SS. It has been reported that miR-146a, -155 and -181a were overexpressed in peripheral blood mononuclear cells (PBMCs) collected from SS patients (7,(10)(11)(12)(13), while miR-17 to -92 were downregulated in the salivary gland tissues (12). Although regulated expression of certain miRNAs have been demonstrated in the salivary gland tissues of SS patients, a comprehensive description of their contribution to the pathological grade of SS remains incomplete.…”

Oral Aspects of Sjögren’s Syndrome

“…The study of Alevizos et al revealed that microRNA are promising candidate biomarkers of inflammation and salivary gland dysfunction in patients with SS (24). Further exploration of the predicted pathways associated with decreased salivary flow in this study will provide insight into the pathophysiology of SS and may identify novel therapeutic targets (24-25).…”