P100 Systemic and local IL-17A and miR-146A levels in rheumatoid arthritis patients
Authors: R Shumnalieva, D Kachakova, T Velikova, S Monov, R Kaneva, Z Kolarov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Assistant. <h3>Introduction</h3> Interleukin 17 (IL-17) is a proinflammatory cytokine, which has been recognized as an important cytokine in the pathogenesis of rheumatoid arthritis (RA).<sup>1</sup> Altered systemic and local expression of specific microRNAs (miRNAs) was been reported in samples of RA patients.<sup>2</sup> 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.<sup>3</sup> <h3>Objectives</h3> 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. <h3>Methods</h3> Expression levels of miR-146a were determined in matched PB and SF samples of RA patients by relative quantitation method 2<sup>-ΔΔCt</sup>. 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 pg/ml versus 0.315 pg/ml, p=0.012). <h3>Conclusions</h3> 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. <h3>References</h3> Gaffen SL. The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. <i>Curr Rheumatol Rep.</i> 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. <i>Arthritis Res Ther.</i> 2008;10:R101. Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, <i>et al</i>. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. <i>BMC Musculoskelet Disord.</i> 2010;11:209. <h3>Acknowledgements</h3> The study was supported by Grant 60/2013 and Grant 61/2015 from Medical University-Sofia, Bulgaria. <h3>Disclosure of Interest</h3> None declared.