ObjectiveMicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren’s syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach.MethodsTwo independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs. A selection of differentially expressed miRNAs was replicated in the second cohort using specific qPCR assays.ResultsA major difference in miRNA expression patterns was observed between the lymphocyte populations from patients with pSS and controls. In CD4 T lymphocytes, hsa-let-7d-3p, hsa-miR-155–5 p, hsa-miR-222–3 p, hsa-miR-30c-5p, hsa-miR-146a-5p, hsa-miR-378a-3p and hsa-miR-28–5 p were significantly differentially expressed in both the discovery and the replication cohort. In B lymphocytes, hsa-miR-378a-3p, hsa-miR-222–3 p, hsa-miR-26a-5p, hsa-miR-30b-5p and hsa-miR-19b-3p were significantly differentially expressed. Potential target mRNAs were enriched in disease relevant pathways. Expression of B-cell activating factor (BAFF) mRNA was inversely correlated with the expression of hsa-miR-30b-5p in B lymphocytes from patients with pSS and functional experiments showed increased expression of BAFF after inhibiting hsa-miR-30b-5p.ConclusionsThis study demonstrates major miRNAs deregulation in T and B cells from patients with pSS in two independent cohorts, which might target genes known to be involved in the pathogenesis of pSS.
BackgroundMicroRNAs (MiRs) play an important role in the pathogenesis of chronic inflammatory diseases. This study is the first to investigate miR expression profiles in purified CD4+ T lymphocytes and CD14+ monocytes from patients with axial spondyloarthritis (axSpA) using a high-throughput qPCR approach.MethodsA total of 81 axSpA patients fulfilling the 2009 ASAS classification criteria, and 55 controls were recruited from October 2014 to July 2017. CD14+ monocytes and CD4+ T lymphocytes were isolated from peripheral blood mononuclear cells. MiR expression was investigated by qPCR using the Exiqon Human MiRnome panel I analyzing 372 miRNAs. Differentially expressed miRNAs identified in the discovery cohort were validated in the replication cohort.ResultsWe found a major difference in miR expression patterns between T lymphocytes and monocytes regardless of the patient or control status. Comparing disease-specific differentially expressed miRs, 13 miRs were found consistently deregulated in CD14+ cells in both cohorts with miR-361-3p, miR-223-3p, miR-484, and miR-16-5p being the most differentially expressed. In CD4+ T cells, 11 miRs were differentially expressed between patients and controls with miR-16-1-3p, miR-28-5p, miR-199a-5p, and miR-126-3p were the most strongly upregulated miRs among patients. These miRs are involved in disease relevant pathways such as inflammation, intestinal permeability or bone formation. Mir-146a-5p levels correlated inversely with the degree of inflammation in axSpA patients.ConclusionsWe demonstrate a consistent deregulation of miRs in both monocytes and CD4+ T cells from axSpA patients, which could contribute to the pathophysiology of the disease with potential interest from a therapeutic perspective.Electronic supplementary materialThe online version of this article (10.1186/s13075-019-1829-7) contains supplementary material, which is available to authorized users.
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