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Int Immunopharmacol ; 63: 35-42, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30075427

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 hsa­miR­432­5p (p < 0.05). We also found upregulation of hsa­miR­194­5p (p < 0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsa­miR­432­5p 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 hsa­miR­432­5p and hsa­miR­194­5p are associated with the regulation of proinflammatory pathways and RA flare-up.


Subject(s)
Antirheumatic Agents/pharmacology , Arthritis, Rheumatoid/genetics , MicroRNAs/blood , Piperidines/pharmacology , Pyrimidines/pharmacology , Pyrroles/pharmacology , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/drug therapy , Female , Humans , Male , Middle Aged , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Recurrence
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