Clinical Rheumatology

, Volume 38, Issue 3, pp 877–884 | Cite as

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

  • Ankita Singh
  • Pradeepta Sekhar Patro
  • Amita AggarwalEmail author
Original Article



Rheumatoid 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).


RA patients (the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria) with active disease (disease-modifying anti-rheumatic drug (DMARD)–naïve and Disease Activity Score 28 (DAS28) > 3.2) were enrolled. They were treated with MTX by gradually increasing dose up to 25 mg/week. After 4 months, 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 4 months after therapy, using hsa-let-7a-5p as housekeeping gene. Results are expressed as median (interquartile range).


The 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 4 months 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).


hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p are potential biomarkers of responsiveness to MTX therapy.


Biomarker Disease-modifying anti-rheumatic drug Methotrexate MicroRNA Rheumatoid arthritis 


Funding statement

The project was funded by a research grant to AA and AS was supported by the Senior Research Fellowship of Indian Council of Medical research.

Compliance with ethical standards



Supplementary material

10067_2018_4380_MOESM1_ESM.pdf (120 kb)
Supplementary Figure 1 Expression level of hsa-miR-132-3p (a), hsa-miR-146a-5p (b) and hsa-miR-155-5p (c) in responders at baseline (n=73) and 4 months after MTX therapy (n-66). Expression level of hsa-miR-132-3p (d), hsa-miR-146a-5p (e) and hsa-miR-155-5p (f) in non-responders at baseline (n=21) and 4 months after MTX therapy (n=14). *P < 0.05, as determined by Mann-Whitney U-test. BL, Baseline; FU, Follow-up; ∆Ct, Delta Threshold Cycle; R, Responder; NR, Non-Responder. (PDF 119 kb)
10067_2018_4380_MOESM2_ESM.pdf (252 kb)
Supplementary Table 1 (PDF 251 kb)


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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  1. 1.Department of Clinical Immunology and RheumatologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia

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