Background MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes. They can regulate the post–transcriptional expression of target genes and play an important role in gene regulation. Specific microRNAs are stably present in serum and changes in their abundance are potentially disease-specific. Considering their important role in regulation of the immune system, we investigated circulating levels of miRNAs in patients with primary Sjögren's syndrome (pSS) and those with non-Sjögren's sicca (nSS) in relation to disease activity.
Objectives To assess the expression of a large number of miRNAs in the serum of pSS and nSS patients as compared to healthy controls and to investigate their correlation with disease activity.
Methods Two independent cohorts (discovery and validation) were established, consisting of a total of 37 pSS patients classified according to the 2002 criteria, 20 nSS patients that were not clinically considered to be pSS and did not meet the classification criteria, and 18 healthy controls (HC). Serum miRNAs were isolated and miRNA profiling of 758 miRNA was performed using the OpenArray platform in the discovery cohort. A selection of 10 miRNAs found to be differentially expressed between the groups was measured in the independent validation cohort using single TaqMan microRNA Assays.
Results miRNA profiling revealed 10 miRNAs to be differentially expressed between the groups; 2 in pSS vs HC, 7 in nSS vs HC and 1 in both pSS and nSS vs HC. One miRNA was excluded from further analysis after technical validation by single TaqMan microRNA Assay. The other 9 miRNAs were measured in the validation cohort. Surprisingly, 2 miRNAs were validated to be increased in the nSS group as compared to HC (snRNA-U6 and miR-661). Using the data from both cohorts combined, the levels of snRNA-U6 and miR-661 was associated with serum Ig and C4 in the nSS group, but also in the pSS group. This prompted us to investigate miRNA expression in subgroups of pSS patients. snRNA-U6 and miR-661 levels are significantly increased compared to HC in pSS patients negative for autoantibodies. In autoantibody positive pSS patients, levels of snRNA-U6 and miR-661 are comparable to those found in HC and both miRNAs are significantly increased in autoantibody negative patients as compared to autoantibody positive pSS patients. In addition, their expression is strongly associated with leukocyte numbers in the autoantibody positive patients, but not in the negative patients.
Conclusions Increased circulating levels of snRNA-U6 and miR-661 in patients with nSS and autoantibody negative pSS patients are associated with normal B cell activity and normal numbers of circulating leukocytes. Reduced miRNA levels in autoantibody positive pSS patients are associated with B cell hyperactivity and decreased leukocyte counts, which is possibly the result of immune cells migration to the inflammatory sites. Considering the important role of miRNAs in the control of immune cell activation, this work points to a significant role of miRNAs in pSS and nSS patients.
Disclosure of Interest None declared
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