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

GABRIEL ADRIÁN RABINOVIC; HÉCTOR TAMASHIRO; JUAN EDUARDO SILVA; GABRIEL ADRIÁN RABINOVIC; HÉCTOR TAMASHIRO; JUAN EDUARDO SILVA; MARÍA SILVIA DI GENARO; RODRIGO BLAS; MABEL NOEMÍ DAVE; MARÍA SILVIA DI GENARO; RODRIGO BLAS; MABEL NOEMÍ DAVE; ALICIA MUNARRIZ; MARÍA GABRIELA LACOSTE; RICARDO JAVIER ELIÇABE ; ALICIA MUNARRIZ; MARÍA GABRIELA LACOSTE; RICARDO JAVIER ELIÇABE

BMC IMMUNOLOGY

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2017 vol. 18 p. 1 - 9

1471-2172

Background:Hyperactivesecretion 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)-1, B-cell-activating factor of the TNF family (BAFF) and anti-lipopolyssacharide (LPS) immunoglobulin (Ig)Awere investigatedby 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-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-17induced anti-LPS IgA production by SFMCs which was independent of IL-6 activity. Concentrations of synovial TGF- and BAFF correlated with anti-LPS and total IgA levels, respectively. Blockade of IL-17 decreased the production of TGF- 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-1 and BAFF may mediate the effect of IL-17 on IgA production. This circuit may contribute to the pathogenesis of inflammatory joint diseases.