AB0078 Systemic and local il-17a and mir-223 levels in rheumatoid arthritis patients. (12th June 2018)

• Record Type: Journal Article
• Authors: Shumnalieva, R.; Kachakova, D.; Velikova, T.; Kaneva, R.; Kolarov, Z.; Monov, S.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 1237
• Page End: 1237
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.5803
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: IL-17 is a proinflammatory cytokine, which overproduction promotes the autoimmune reaction in rheumatoid arthritis (RA). Recent studies have shown that IL-17 production in lymphocytes or its function could be regulated by miR-223 by targeting Roquin ubiquitin ligase or its receptors 1–4 . Objectives: To examine a possible correlation between the expression levels of miR-223 and IL-17A in peripheral blood (PB) and synovial fluid (SF) of RA patients. Methods: Expression levels of miR-223 were determined in matched PB and SF samples of RA patients by relative quantitation method 2 -ΔΔCt . As reference control for normalisation RNU6B gene was used. 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 healthy control (HCs) as well as within the RA group. Results: 58, 73% of the RA patients showed overexpression of miR-223 in PB when compared to HCs (p=0.008) with AUC=0.673 (95 CI: 0.562/0.784), with 71.4% sensitivity and 46.9% specificity (p=0.006). miR-223 was overexpressed in 79.17% of RA SF (p=1.64 × 10–3) when compared to HCs SF with AUC=0.841 (95 CI: 0.724/0.958) with 87.5% sensitivity and 72.7% specificity (p=4.6 × 10–4). Within the RA group, 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). Conclusions: The difference between the systemic and local levels of miR-223 and IL17A in RA patients shows that the inflammatory disease process leads to their altered expression with a possible role of both molecules in the disease pathogenesis. The opposite changes in their systemic and local levels confirm the data about the possible role of miR-223 in regulating IL-17 function. References: [1] Haneklaus M, Gerlic M, O'Neill LA, Masters SL. miR-223: infection, inflammation and cancer. J Intern Med. 2013;274(3):215–226. [2] Khan D, Ansar Ahmed SA. Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs. Front Genet. 2015;6:236. [3] Moriya N, Shibasaki S, Karasaki M, Iwasaki T. The Impact of MicroRNA-223–3p on IL-17 Receptor D Expression in Synovial Cells. PLoS One2017;12(1):e0169702. [4] 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 Immunol2013;190(1 Supplement):171.9. Acknowledgements: The study was supported by Grant 14D/2012 and Grant 61/2015 funded by Medical University-Sofia, Bulgaria Disclosure of Interest: None declared