MicroRNAs (miRNAs) are small non-coding single-stranded RNAs of about 22 nucleotides in length that act as post-transcriptional regulators of gene expression. Depending on the complementarity between miRNA and target mRNA, cleavage, destabilization, or translational suppression of mRNA occurs within the RISC (RNA-induced silencing complex). As gene expression regulators, miRNAs are involved in a variety of biological functions. Dysregulation of miRNAs and their target genes contribute to the pathophysiology of many diseases, including autoimmune and inflammatory disorders. MiRNAs are also present extracellularly in their stable form in body fluids. Their incorporation into membrane vesicles or protein complexes with Ago2, HDL, or nucleophosmin 1 protects them against RNases. Cell-free miRNAs can be delivered to another cell in vitro and maintain their functional potential. Therefore, miRNAs can be considered mediators of intercellular communication. The remarkable stability of cell-free miRNAs and their accessibility in body fluid makes them potential diagnostic or prognostic biomarkers and potential therapeutic targets. Here we provide an overview of the potential role of circulating miRNAs as biomarkers of disease activity, therapeutic response, or diagnosis in rheumatic diseases. Many circulating miRNAs reflect their involvement in the pathogenesis, while for plenty, their pathogenetic mechanisms remain to be explored. Several miRNAs described as biomarkers were also shown to be of therapeutic potential, and some miRNAs are already tested in clinical trials.

• Keywords
• Biomarker, Diagnosis, Rheumatic diseases, Therapy, miRNA,
• Publication type
• Journal Article MeSH
• Review MeSH

Circulating miRNAs appear promising therapeutic and prognostic biomarkers. We aimed to investigate the predictive value of circulating miRNAs on the disease outcome following anti-TNF therapy in patients with ankylosing spondylitis (AS). Our study included 19 AS patients assessed at baseline (M0), after three (M3) and twelve months (M12) of therapy. Total RNA was isolated from plasma. A comprehensive analysis of 380 miRNAs using TaqMan Low Density Array (TLDA) was followed by a single assay validation of selected miRNAs. All AS patients had high baseline disease activity and an excellent response to anti-TNF therapy at M3 and M12. TLDA analysis revealed the dysregulation of 17 circulating miRNAs, including miR-145. Single assay validation confirmed that miR-145 is significantly downregulated at M3 compared to baseline. The decrease in the levels of miR-145 from M0 to M3 negatively correlated with the change in BASDAI from M0 to M3; and positively correlated with disease activity improvement from M3 to M12 as per BASDAI and ASDAS. The predictive value of the early change in miR-145 and levels of miR-145 at M3 were further validated by Receiver operating curves analysis. We show thatthe early change in circulating miR-145 may be a predictor for the future outcome ofAS patients treated with TNF inhibitors. Patients with a more significant decrease in miR-145 levels may show further significant improvement of disease activity after 12 months. Monitoring the expression of miR-145 in plasma in AS patients may, therefore, influence our therapeutic decision-making.

• MeSH
• Spondylitis, Ankylosing blood   diagnosis   drug therapy   immunology   MeSH
• Biomarkers blood   MeSH
• Time Factors MeSH
• Circulating MicroRNA blood   MeSH
• Adult MeSH
• Tumor Necrosis Factor Inhibitors adverse effects   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• MicroRNAs blood   MeSH
• Young Adult MeSH
• Tumor Necrosis Factor-alpha antagonists & inhibitors   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• Circulating MicroRNA MeSH
• Tumor Necrosis Factor Inhibitors MeSH
• MicroRNAs MeSH
• MIRN145 microRNA, human MeSH Browser
• TNF protein, human MeSH Browser
• Tumor Necrosis Factor-alpha MeSH