Background/Purpose: Systemic sclerosis (SSc) is an autoimmune rheumatic and musculoskeletal disease (RMD) with a high mortality. Epigenetic factors, such as miRNAs might play an important role in the pathogenesis of SSc. In this cross-sectional study we assessed miRNA in SSc and associated miRNA expression with disease-related organ manifestations.

Methods: We investigated the miRNA profiles of 52 SSc patients (42 women and 10 men; mean age: 59.1 years (range: 33-76 years). Anticoagulated blood samples were taken from SSc patients, as well as age- and gender-matched healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated on a Ficoll gradient, stored in TRIzol at -20°C until use. Total RNA was purified. Sequencing of miRNAs was performed using high-throughput, new generation (Illumina) sequencing, and an established miRNA library.

Results: Altogether 58 miRNAs showed significantly differential expression in SSc patients compared to controls. Among these miRNAs, 34 were significantly upregulated and 24 downregulated. Out of the differentially expressed miRNAs, 9 upregulated (let-7e-3p, miR-16-1-3p, miR-16-2-3p, miR-27a-5p, miR-34c-5p, miR-92a-1-5p, miR-130b-5p, miR-143-5p, miR-183-5p) and 8 downregulated miRNAs (miR-7-1-3p, miR-17-5p, miR-20a-5p, miR-30b-5p, miR-106a-5p, miR-151a-5p, miR-320b és miR-335-5p) had previously been described in the literature. Thus, the differential expression of further 41 (25 upregulated and 16 downregulated) miRNAs is a novel finding. When comparing SSc patients with (n=34) and without (n=18) interstitial lung disease (ILD)/pulmonary fibrosis, 4 miRNAs (miR-210-3p, miR-222-3p, miR-379-5p, miR-3935-5p) showed elevated, while 4 miRNAs (miR-125a-5p, miR-199b-5p, miR-941, miR-1226-3p) showed decreased expression levels in patients with SSc-ILD. Some of the differentially expressed miRNAs are associated with TGFβ signalling pathways.

Conclusion: SSc is associated with differential expression of several miRNAs. The up- or down-regulated expression of some miRNAs might be associated with SSc-ILD. Thus, miRNAs might have an important role in the molecular pathogenesis of SSc, as well as SSc-ILD and some of them might serve as therapeutic targets as well.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-mirna-patterns-of-peripheral-blood-mononuclear-cells-show-correlations-with-pulmonary-manifestations-of-systemic-sclerosis/