Background New insights into the molecular mechanisms in rheumatoid arthritis (RA) reveal the important role of microRNAs (miRNAs) in the disease pathogenesis. miRNAs comprise a class of small non-coding RNAs that negatively regulate gene expression at posttranscriptional level. It has been proven that the altered expression of certain miRNAs in RA leads to dysregulation of the immune system, cytokine production and initiation and perpetuation of the disease process. Due to their stability miRNAs are widely explored as potential biomarkers for RA disease activity and treatment response.
Objectives The objective of our study was to evaluate the role of expression levels of microRNA-155 (miR-155) in the synovial fluid (SF) of RA patients as diagnostic and prognostic biomarker in the clinical practice.
Methods 46 RA patients selected according to the 1987 ACR criteria and 22 healthy controls (22) were included in the study. miR-155 expression levels in SF samples were analyzed through real-time PCR (SYBR Green technology) and ΔΔCt method was performed.
Results miR-155 showed statistically significant overexpression in SF from RA patients when compared to HCs (p<0.05). Receiver operating characteristic (ROC) curve analysis was constructed in order to evaluate the diagnostic accuracy of the expression levels of miR-155 in SF. Area under the curve (AUC) was 0.865 (95 CI: 0,770 - 0,961) with 80.9% sensitivity and 79.1% specificity when the RQ cut value was 2.1. Levels of miR-155 in SF showed correlation with clinical markers for disease activity such as swollen joint count (p=0.036 two tailed), tender joint count (p=0.020 two tailed), VAS (p=0.014 two tailed) and DAS28 (p=0.015 two tailed) with Spearman's correlation coefficients 0.274, 0.303, 0.319 and 0.314 respectively.
Conclusions SF miR-155 is a potential biomarker for diagnosis of RA with high levels of sensitivity and specificity. Expression levels of miR-155 correlate with number of swollen and tender joints as well as DAS28 and it is a possible local biomarker for disease activity in the clinical practice.
Kurowska-Stolarska M, Alivernini S, Ballantine LE, DL Asquith, Millar NL, Gilchrist DS et al. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis, Proc. Natl. Acad. Sci. USA, 2011;108(27):11193-11198.
Leah E. Rheumatoid arthritis: miR-155 mediates inflammation, Nat. Rev. Rheumatol., 2011;7(8):437.
Murata K, Yoshitomi H, Tanida S, Ishikawa M, Nishitani N, Ito H, Nakamura T. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis, Arthritis. Res. Ther. 2010;12(3):86.
Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling O, Gay RE et al. Altered expression of microRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis, Arthritis Rheum., 2008;58(4):1001-1009.
Acknowledgements The study was supported by Grant 55/2013 funded by Medical University – Sofia, Bulgaria
Disclosure of Interest None declared