MicroRNA-132, miR-146a, and miR-155 as potential biomarkers of methotrexate response in patients with rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) patients have high expression levels of hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p in peripheral blood. We studied if baseline blood levels of these microRNAs (miRNAs) could predict response to methotrexate (MTX).MethodsRA patients (the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria) with active disease (disease-modifying anti-rheumatic drug (DMARD)-naive and Disease Activity Score 28 (DAS28) >3.2) were enrolled. They were treated with MTX by gradually increasing dose up to 25mg/week. After 4months, the DAS28 score was calculated and EULAR response was assessed. The hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p levels were measured by real-time qPCR in whole-blood RNA at baseline and 4months after therapy, using hsa-let-7a-5p as housekeeping gene. Results are expressed as median (interquartile range).ResultsThe 94 enrolled patients (81 females) had a median age of 40 (17) years, disease duration of(24)months, and DAS28 4.61 (1.11). After 4months of therapy, 73 were classified as responders and 21 as non-responders. Baseline levels of all three miRNAs were lower in responders than non-responders, hsa-miR-132-3p (-8.03 (0.70) versus -7.47 (0.85), P<0.05), hsa-miR-146a-5p (-5.11 (0.88) versus -4.62 (0.90), P<0.05), and hsa-miR-155-5p (-7.59 (1.07) versus -7 (0.72), P=0.002). Receiver operating characteristic curve analysis showed that all three miRNAs were also good predictors of MTX response, showing the following values: hsa-miR-132-3p (area under curve (AUC) 0.756, P<0.05), hsa-miR-146a-5p (AUC 0.760, P<0.05), and hsa-miR-155-5p (AUC 0.728, P=0.002).Conclusionhsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p are potential biomarkers of responsiveness to MTX therapy.