Annals of the Rheumatic Diseases | 2019
P100\u2005Systemic and local IL-17A and miR-146A levels in rheumatoid arthritis patients
Abstract
Career situation of first and presenting author Assistant. Introduction Interleukin 17 (IL-17) is a proinflammatory cytokine, which has been recognized as an important cytokine in the pathogenesis of rheumatoid arthritis (RA).1 Altered systemic and local expression of specific microRNAs (miRNAs) was been reported in samples of RA patients.2 It has been found that miR-146a was associated with IL-17 expression in IL-17 producing T-cells in the synovium thus indicating its possible role in RA pathogenesis via IL-17 expression.3 Objectives To examine a possible deregulation of the expression levels of miR-146a and levels of IL-17A in peripheral blood (PB) and synovial fluid (SF) of RA patients. Methods Expression levels of miR-146a were determined in matched PB and SF samples of RA patients by relative quantitation method 2-ΔΔCt. As reference control for normalization RNU6B gene was used. Receiver operating characteristic (ROC) curve analysis using RQ values was constructed in order to evaluate the diagnostic accuracy of miR-146a in PB and SF for distinguishing RA patients from healthy controls (HCs). Concentrations of IL-17A in matched serum and SF samples were determined by Human IL-17A ELISA kit (Gene probe, Diaclone). The results were compared to HCs as well as within the RA group. Results miR-146a was overexpressed in 70.83% of RA SF (p=0.007) when compared to HCs SF. The ROC curve analysis showed diagnostic accuracy for miR-146a in SF with AUC=0.769 (95 CI: 0.600÷0.938) with 75.0% sensitivity and 72.3% specificity (p=0.006). SF levels of miR-146a were overexpressed in 52.17% of the RA patients compared to its systemic levels. Levels of IL-17A were higher in RA SF compared to serum (8.645\u2009pg/ml versus 0.315\u2009pg/ml, p=0.012). Conclusions The difference between the systemic and local levels of miR-146a and IL-17A in RA patients indicates that the local inflammatory process leads to their deregulation with a possible role of both molecules in the disease pathogenesis. The higher local levels of miR-146a and IL-17A suggest the possible relationship between miR-146a expression and the production of IL-17 from IL-17 expressing cells. References Gaffen SL. The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Curr Rheumatol Rep. 2009;11(5):365–70. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008;10:R101. Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord. 2010;11:209. Acknowledgements The study was supported by Grant 60/2013 and Grant 61/2015 from Medical University-Sofia, Bulgaria. Disclosure of Interest None declared.