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

I Alevizos, S Alexander, RJ Turner… - Arthritis & …, 2011 - Wiley Online Library
I Alevizos, S Alexander, RJ Turner, GG Illei
Arthritis & Rheumatism, 2011Wiley Online Library
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 …
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 accu-rately 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 pat-terns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers.
Sjögren’s syndrome (SS) is characterized by features of systemic autoimmunity and exocrine gland dysfunction and inflammation. The exact cause of exocrine gland dysfunction in SS has not been delineated, but it is thought that both immunologically mediated and nonimmune mechanisms contribute significantly (1). The diagnosis of SS is based on the combination of symptoms and signs of dry mouth and/or dry eyes, the presence of autoantibodies, and an inflammatory infiltrate in the minor salivary glands (MSGs). The intensity of the infiltrate varies considerably and is described by the focus score, which can range from 0 to 12, with the highest score representing diffuse lymphocytic infiltrates. There is also a great deal of variation in salivary flow, ranging from essentially normal production to no production of saliva. The correlation between the focus score and salivary flow is poor, suggesting that these may be 2 independent processes. Alternatively, the poor correlation between the focus score and salivary flow may reflect the limitations of our current methods, which rely solely on quantitative assessments of inflammation and dysfunction. More sophisticated biomarkers that reliably describe the different pathophysiologic aspects of SS are needed to establish the diagnosis, ClinicalTrials. gov identifiers: NCT00001852, NCT00001196, NCT0001390.
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