Ankita Singh1, Pradeepta Sekhar Patro1, Amita Aggarwal2. 1. Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India. 2. Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India. aa.amita@gmail.com.
Abstract
INTRODUCTION: 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). METHODS: 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). RESULTS: 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). CONCLUSION: hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p are potential biomarkers of responsiveness to MTX therapy.
INTRODUCTION: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). METHODS:RApatients (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). RESULTS: 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). CONCLUSION: hsa-miR-132-3p, hsa-miR-146a-5p, and hsa-miR-155-5p are potential biomarkers of responsiveness to MTX therapy.
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