Changes in MiRNA-5196 Expression as a Potential Biomarker of Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis Patients

Abstract

In this study, we analysed the expression level of sera circulating miRNA-5196 in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients before and after tumor necrosis factor (TNF)-α therapy as biomarkers predicting positive treatment outcome. We enrolled 10 RA patients, 13 AS patients, and 12 healthy individuals in the study. The expression of miRNA-5196 was measured by real-time polymerase chain reaction before and after anti-TNF-α therapy. Disease activity of RA patients was assessed using disease activity score 28 (DAS28), whereas ankylosing spondylitis DAS (ASDAS) was used in AS patients. MiRNA-5196 expression was significantly higher in patients with RA and AS before TNF-α therapy than in those following anti-TNF-α therapy and healthy controls. Changes in miRNA-5196 expression positively correlated with delta DAS28 or delta ASDAS, respectively, following TNF-α therapy. In contrast, changes in C-reactive protein (CRP) levels in RA and AS patients did not positively correlate with DAS28 or ASDAS changes. Receiver-operating characteristic analysis showed better diagnostic accuracy of miRNA-5196 expression both in RA (area under curve (AUC) = 0.87, p = 0.055) and AS patients (AUC = 0.90, p = 0.050) compared to CRP levels in RA (AUC = 0.75, p = 0.201) and AS patients (AUC = 0.85, p = 0.086) upon biologic therapy treatment. Finding novel biomarkers, including miRNA-5196 which allow to predict and monitor anti-TNF-α response, would be of clinical value especially during the early phase of RA or AS development.

MiR-140-3p inhibits the cell viability and promotes apoptosis of synovial fibroblasts in rheumatoid arthritis through targeting sirtuin 3

“…Although lots of studies have shown that miRNA plays a crucial part in the progress of many kinds of cancer, evidences also showed that the abnormal expression of miRNAs in autoimmune diseases is not only an accidental event [ 10 , 19 – 21 ]. Studies from different research teams have shown that miRNAs were widely involved in the regulation of RA pathological and physiological processes, and play an important role in the proliferation, apoptosis, and inflammatory cascade reaction of different SF cells in RA, including miR-613, miR-126, miR-140-5p, miR-451, and so on [ 4 , 8 , 12 , 22 ].…”

Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity

“…Based on the hypothesis that anti-TNFα therapy might de-regulate miRNA expression, we first analyzed those studies that evaluated the miRNA expression in patients treated with anti-TNFα, and then compared the de-regulated miRNA with the PDAC findings reported in the DBDEMC2 database (see Table 2). Some studies in the literature report on the up- or down-regulation of miRNA following anti-TNFα therapy [94,95,96,97,98,99,100]. Notably, some miRNA (i.e., hsa-let-7d, hsa-miR-221, hsa-miR-224, hsa-miR-23a, and hsa-miR-197) were found to be up-regulated by anti-TNFα, and are reportedly associated with pancreatic cancer [91,101].…”

DNA Methylation as a Future Therapeutic and Diagnostic Target in Rheumatoid Arthritis

“…In contrast, Zhu et al reported that miRNA-23b inhibited IL-17-associated inflammation by targeting TGF- β binding protein 2 (TAB2) and TAB3 [18]. Our recent results demonstrated that sera circulating miRNA-5196 could be used as a biomarker predicting positive treatment outcome of TNF-α therapy in RA and ankylosing spondylitis patients, whereas single-nucleotide polymorphisms (SNPs) of miRNA-146a contribute to RA development [2,83]. Similarly, using genome-wide association study (GWAS) data, Wohlers et al reported that SNP rs968567 affected the expression of miR-1908-5p and contributed to RA predisposition [84].…”