Abstract
BackgroundHyperactive secretion and pathogenic effects of interleukin (IL)-17 and IgA have been detected in different arthropathies. Recent evidence has revealed that TH17 cytokines regulate mucosal IgA secretion. However, it is unknown whether and how IL-17 mediates synovial IgA production. Here we aim to investigate the connection of synovial IL-17 with IgA production in the joint.In this study we included synovial fluids (SF) from patients with rheumatoid arthritis (RA; n = 66), spondyloarthritis (SpA; n = 18) and osteoarthritis (OA; n = 36). The levels of IL-17, IL-6, transforming growth factor (TGF)-β1, B-cell-activating factor of the TNF family (BAFF) and anti-lipopolyssacharide (LPS) immunoglobulin (Ig)A were investigated by enzyme-linked immunosorbent assay (ELISA). Total IgA was measured by radial immunodiffusion assay. Synovial fluid-derived mononuclear cells (SFMC) were stimulated with bacterial antigens or SF-conditioned media, and cytokines and IgA were analyzed in the supernatants.ResultsIL-17, IL-6 and TGF-β1 were increased in SF from both RA and SpA compared with OA patients. Concentration of IL-17 correlated with the disease activity score (DAS)-28, IL-6 and anti-LPS IgA levels. Bacterial-stimulated SFMCs from RA and SpA patients secreted higher IL-17 than vehicle-stimulated SFMCs. Conditioned media with SF containing IL-17 induced anti-LPS IgA production by SFMCs which was independent of IL-6 activity. Concentrations of synovial TGF-β1 and BAFF correlated with anti-LPS and total IgA levels, respectively. Blockade of IL-17 decreased the production of TGF-β1 and anti-LPS IgA by SF-stimulated SFMCs.ConclusionsThis study reports a connection between IL-17 and IgA secretion in the joint. In addition, it demonstrates that enterobacterial antigens trigger synovial IL-17 production, and that TGF-β1 and BAFF may mediate the effect of IL-17 on IgA production. This circuit may contribute to the pathogenesis of inflammatory joint diseases.
Highlights
Hyperactive secretion and pathogenic effects of interleukin (IL)-17 and immunoglobulin A (IgA) have been detected in different arthropathies
Synovial IL-17, IL-6 and transforming growth factor-β1 (TGF-β1) production in patients with rheumatoid arthritis (RA) and SpA Since IL-17 has been associated with the pathogenesis of RA and SpA [32, 33], we first studied this cytokine in synovial fluids (SF) from RA and SpA in comparison with OA patients
We found a higher number of patients with detectable synovial IL-17 in RA and SpA compared to OA (62% and 59%, respectively versus 5.5%) (P < 0.0001 compared with OA for both comparisons)
Summary
Hyperactive secretion and pathogenic effects of interleukin (IL)-17 and IgA have been detected in different arthropathies. Recent evidence has revealed that TH17 cytokines regulate mucosal IgA secretion It is unknown whether and how IL-17 mediates synovial IgA production. Rheumatoid arthritis (RA), one of the most common autoimmune osteoarticular diseases, is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and systemic disorders mainly driven by pro-inflammatory cytokines and matrix-degrading enzymes [13]. Infectious agents and their products have been largely linked with RA the precise mechanisms implicated in this complex relationship is not fully understood [11, 12, 14]. Whether enterobacterial antigens trigger synovial IL-17 in RA and SpA is still uncertain
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