TY - JOUR T1 - IL-17A and IL-17F expression and functional responses in rheumatoid arthritis and peripheral spondyloarthritis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.190571 SP - jrheum.190571 AU - Sijia Chen AU - Iris Blijdorp AU - Leonieke van Mens AU - Rowann Bowcutt AU - Talia Latuhihin AU - Marleen van de Sande AU - Stevan Shaw AU - Nataliya Yeremenko AU - Dominique Baeten Y1 - 2020/01/15 UR - http://www.jrheum.org/content/early/2020/01/10/jrheum.190571.abstract N2 - Objective Targeting the IL-17-axis is efficacious in psoriasis (PsO) and spondyloarthritis (SpA) but not in rheumatoid arthritis (RA). We investigated potential differences in tissue expression and function of IL-17A and IL-17F in these conditions. Methods mRNA expression of cytokines and their receptors was assessed by qPCR in psoriasis skin, in SpA and RA synovial tissue (ST) and fibroblast-like synoviocytes (FLS). Cytokines were measured in synovial fluid (SF) and FLS supernatants by ELISA. FLS were stimulated with IL-17A or IL-17F cytokines supplemented with TNF, or with pooled SF from SpA or RA patients. Results IL-17A (p=0.031) and IL-17F (p=0.017) mRNA were lower expressed in psoriatic ST versus paired psoriasis skin. IL-17A mRNA was 2.7-fold lower expressed than IL-17F in skin (p=0.0078) but 17.3-fold higher in ST (p<0.0001). In SF, IL-17A protein was 37.4-fold higher than IL-17F (292.4(81.4-464.2) vs 7.8(7.7-8.7) pg/ml, p<0.0001). IL-17A and IL-17F mRNA and protein levels did not differ in SpA versus RA synovitis. Neither were IL-17RA, IL-17RC (IL-17-receptors), TNFRI and TNRII (TNF-receptors) differentially expressed between SpA and RA ST, nor between SpA and RA FLS. SpA and RA FLS produced similar amount of IL-6 and IL-8 protein upon stimulation with IL-17A or IL-17F, supplemented with 1 ng/ml TNF. Pooled SpA or RA SF enhanced FLS inflammatory response to IL-17A and IL-17F similarly. Conclusion The IL-17A/IL-17F expression ratio is higher in SpA synovitis compared to psoriasis skin. Expression of IL-17A and IL-17F, and the functional response to these cytokines, however, appear to be similar in SpA and RA synovitis. ER -