Association between IL-17 and IgA in the joints of patients with inflammatory arthropathies

作者：Elicabe Ricardo Javier; Silva Juan Eduardo; Dave Mabel Noemi; Lacoste Maria Gabriela; Tamashiro Hector; Blas Rodrigo; Munarriz Alicia; Rabinovich Gabriel Adrian; Di Genaro Maria Silvia

来源：BMC IMMUNOLOGY, 2017, 18(1): 8.

DOI：10.1186/s12865-017-0189-9

• Interleukin-17
• Immunoglobulin A
• Synovial fluid
• Transforming growth factor
• B-cell activating factor of the TNF family

Background: Hyperactive secretion and pathogenic effects of interleukin (IL)-17 and IgA have been detected in different arthropathies. Recent evidence has revealed that T(H)17 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)-beta(1), 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.
Results: IL-17, IL-6 and TGF-beta(1) 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-beta(1) and BAFF correlated with anti-LPS and total IgA levels, respectively. Blockade of IL-17 decreased the production of TGF-beta(1) and anti-LPS IgA by SF-stimulated SFMCs.
Conclusions: This 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-beta(1) and BAFF may mediate the effect of IL-17 on IgA production. This circuit may contribute to the pathogenesis of inflammatory joint diseases.

• 出版日期2017-2-6