Analysis of miRNA expression in patients with rheumatoid arthritis during remission and relapse after a 5-year trial of tofacitinib treatment.

Abstract The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5-year open-label clinical trial) and to describe the expression of miRNAs during RA remission or flare-up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Student's t -test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsa‑miR‑432‑5p ( p < 0.05). We also found upregulation of hsa‑miR‑194‑5p ( p < 0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsa‑miR‑432‑5p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsa‑miR‑432‑5p and hsa‑miR‑194‑5p are associated with the regulation of proinflammatory pathways and RA flare-up. Highlights • hsa‑miR‑432‑5p is downregulated in patients achieving clinical remission. • Treatment with Tofacitinib does not affect miRNA expression directly. • Patients with relapse have a specific miRNA signature as measured by Firefly Bioworks. • hsa‑miR‑194-5p is upregulated during RA flare-up patients suggesting that this miRNA could be used as a biomarker for relapse. [ABSTRACT FROM AUTHOR]