AB0020 CORRELATION BETWEEN SERUM AND SYNOVIAL CONCENTRATION OF IL-17A AND MIRNA EXPRESSION IN RHEUMATOID ARTHRITIS PATIENTS
Authors: R. Shumnalieva, D. Kachakova, T. Velikova, R. Kaneva, Z. Kolarov, S. Monov
Journal: Annals of the Rheumatic Diseases (2020)

Background: Interleukin 17 (IL-17) is a proinflammatory cytokine, which overproduction promotes the autoimmune reaction in rheumatoid arthritis (RA). Posttranscriptional regulation of IL-17 by specific microRNAs (miRNAs) is of great interest in the recent years. 146a was associated with IL-17 expression in IL-17 producing T-cells in the synovium when miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by directly targeting the suppressor of cytokine signaling (SOCS) 1 [1, 2]. It has been shown that IL-17 production in lymphocytes or its function could be regulated by miR-223 by targeting Roquin ubiquitin ligase or its receptors [3]. Objectives: To examine a possible correlation between systemic and local concentrations of IL-17A and systemic and local miR-146a, miR-155 and miR-223 expression in RA patients. Methods: Expression levels of three miRNAs were determined in matched peripheral blood (PB) and synovial fluid (SF) samples of RA patients by relative quantitation method 2 -ΔΔCt . As reference control for normalization RNU6B gene was used. Concentrations of IL-17A were compared between matched serum and SF samples from 20 RA patients by Human IL-17A ELISA kit (Gene probe, Diaclone, France). Healthy donors were used as controls. Results: miR-146a, miR-155 and miR-223 showed overexpression in RA SF when compared to HCs SF (in 70.83%, p=0.007; in 79.17%, p=1.63x10 -4 and in 79.17%, p=1.64x10 -3 , respectively). The ROC curve analysis showed diagnostic accuracy for miR-146a in SF with AUC=0.769, p=0.006, AUC for SF miR-155 was 0.858, p=2.3x10 -4 and AUC for SF miR-223 was 0.841 p=4.6x10 -4 . SF levels of miR-146a and miR-155 were overexpressed in 52.17% and in 76.09% of the RA patients compared to its systemic levels. SF miR-223 was underexpressed in 58.7% of the 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). ROC curve analysis for SF IL-17A showed area under the curve (AUC) = 0.885, p&lt;0.000. Conclusion: The difference between the systemic and local concentration of IL-17A and miRNAs expression shows that the inflammatory disease process leads to their altered expression with a possible role of these molecules in the disease pathogenesis. The higher local levels of miR-155, miR-146 and IL-17A confirm the data about the possible role of these miRNAs in regulating IL-17A production. The opposite changes of IL-17A and miR-223 systemic and local levels confirm the data about the possible role of miR-223 in regulating IL-17 function. Further analysis with larger sets is needed to confirm these results. References: [1]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. [2]Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X. et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE 2012; 7(10):e46082. [3]Schaefer J, Nakra N, Montufar-Solis D, Vigneswaran N, Klein J. Role for miR-223 and Roquin in IL-10 mediated regulation of IL-17. J Immunol. 2013; 190 (1 Supplement) 171.9. Acknowledgments: The study was supported by Grant 14-D/2012, Grant 60/2013 and Grant 61/2015 from Medical University-Sofia, Bulgaria Disclosure of Interests: None declared