Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study

Abstract

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: This study aimed to explore the correlation of circulating microRNA (miRNA) expression profile with clinical response to tumor necrosis factor (TNF) inhibitor in treating rheumatoid arthritis (RA) patients. Methods: Baseline PBMC samples from eight responders and eight non-responders after 24-week TNF inhibitor (etanercept) treatment were subjected to miRNA microarray. Then, top 10 dysregulated miRNAs were selected and further validated by quantitative polymerase chain reaction (qPCR) in baseline PBMC samples from 92 RA patients treated with 24-week TNF inhibitor (etanercept). Responders and nonresponders were divided referring to the decline in disease activity score in 28 joints.Results: In microarray assay, total 59 upregulated and 78 downregulated miRNAs were identified in responders compared to non-responders, which were mainly enriched in regulating immune-and inflammation-related biological processes and pathways. The top 10 dysregulated miRNAs were as follows: miR-192-5p, miR-146a-5p, miR-19b-3p, miR-320c, miR-335-5p, miR-149-3p, miR-766-3p, let-7a-5p, miR-24-3p, and miR-1226-5p. In qPCR validation, miR-146a-5p was increased, while let-7a-5p was decreased in responders compared with non-responders. Multivariate logistic analysis illuminated that miR-146a-5p and CRP independently correlated with higher clinical response, while let-7a-5p and biologics history independently associated with lower clinical response. Subsequently, receiver operating characteristic curve showed that combination of these four independent factors presented with a great predictive value for clinical response with area under curve: 0.863, 95% CI 0.781-0.945.Conclusion: miRNA expression profile is closely implicated in the treatment efficacy of TNF inhibitor, and combined measurement of miR-146a-5p, let-7a-5p, CRP, and biologics history disclosed a great predictive value for clinical response to TNF inhibitor in RA patients. How to cite this article: Liu Y, Han Y, Qu H, Fang J, Ye M, Yin W. Correlation of microRNA expression profile with clinical response to tumor necrosis factor inhibitor in treating rheumatoid arthritis patients: A prospective cohort study.

Analysis of miRNA Expression in Patients with Rheumatoid Arthritis during Olokizumab Treatment

“…As olokizumab acts as inhibitor of IL-6/IL-6R, we proposed that prognostic potential of these miRNAs in olokizumab treatment could be in part associated with their effect on the signaling pathway. [19] decreased SF -biomarker of therapy with TNF inhibitors response [31] miR-137 decreased SF CXCL12 regulate proliferation, migration and invasion [32] miR-26b decreased SF GSK-3P…”

Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

“…Serum level of miR-5196 is significantly decreased in RA and AS patients after anti-TNF-α therapy and indicates a lower DAS28 scores (95). Meanwhile, serum level of miR-146a are showed decreased in RA patients who responded well to anti-TNF therapy and showed interesting response prediction ability to anti-TNF-α therapy (24,96,97) together with CRP. In contrast, serum level of miR-23 and miR-223 are increased in RA patients who response well to anti-TNF-α/DMARD combination therapy, while negative correlated to the response to anti-TNF drugs (96).…”

The Potential Importance of MicroRNAs as Novel Indicators How to Manage Patients with Juvenile Idiopathic Arthritis More Effectively

“…It also targets IL-1 receptor-associated kinase 1 and 2 (IRAK1, IRAK2) as well as tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) [ 30 ], which enables suppression of NFkB signaling [ 3 ] and modulation of TNF production [ 31 ]. Furthermore, miR-146a promotes the expression of proinflammatory cytokines (including, among others, IL-2 and IL-12) by its upregulation in Th1 [ 32 ] and Th17 lymphocytes [ 24 ] with concurrent downregulation in Th2 cells [ 33 ]. Despite being decreased in early RA when compared to the patients with established diagnosis [ 34 ], miR-146a was found to be elevated in oligo-, polyarticular, and SoJIA [ 17 , 28 ].…”