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



IL-17, IL-6 and TGF-β1were 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-β1and BAFF correlated with anti-LPS and total IgA levels, respectively. Blockade of IL-17 decreased the production of TGF-β1and anti-LPS IgA by SF-stimulated SFMCs.



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-β1and BAFF may mediate the effect of IL-17 on IgA production. This circuit may contribute to the pathogenesis of inflammatory joint diseases.
Division of Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, Ejército de los Andes 950, San Luis, Argentina.|Laboratory of Immunopathology, Multidisciplinary Institute of Biological Investigations - San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations (CONICET), Ejército de los Andes 950, San Luis, 5700, Argentina.
Ricardo Javier
RJ
Eliçabe
Division of Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, Ejército de los Andes 950, San Luis, Argentina.|Laboratory of Immunopathology, Multidisciplinary Institute of Biological Investigations - San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations (CONICET), Ejército de los Andes 950, San Luis, 5700, Argentina.
Juan Eduardo
JE
Silva
Division of Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, Ejército de los Andes 950, San Luis, Argentina.|Laboratory of Immunopathology, Multidisciplinary Institute of Biological Investigations - San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations (CONICET), Ejército de los Andes 950, San Luis, 5700, Argentina.
Mabel Noemí
MN
Dave
Division of Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, Ejército de los Andes 950, San Luis, Argentina.|Laboratory of Immunopathology, Multidisciplinary Institute of Biological Investigations - San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations (CONICET), Ejército de los Andes 950, San Luis, 5700, Argentina.
María Gabriela
MG
Lacoste
Private Medical Clinic Bolivar, Bolivar 1277, San Luis, 5700, Argentina.
Héctor
H
Tamashiro
Medical Clinic Medici, Ayacucho 1118, San Luis, 5700, Argentina.
Rodrigo
R
Blas
CENYR Center, Ituzaingo 1074, San Luis, 5700, Argentina.
Alicia
A
Munarriz
Laboratory of Immunopathology, Institute of Biology and Experimental Medicine (IBYME), CONICET, Vuelta de Obligado 2490, Buenos Aires, C1428A, Argentina.|Faculty of Exact and Natural Sciences, University of Buenos Aires, Intendente Güiraldes 2160, Buenos Aires, C1428EGA, Argentina.
Gabriel Adrián
GA
Rabinovich
Division of Immunology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, Ejército de los Andes 950, San Luis, Argentina. sdigena@unsl.edu.ar.|Laboratory of Immunopathology, Multidisciplinary Institute of Biological Investigations - San Luis (IMIBIO-SL), National Council of Scientific and Technical Investigations (CONICET), Ejército de los Andes 950, San Luis, 5700, Argentina. sdigena@unsl.edu.ar.
María Silvia
MS
Di Genaro
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053264:B-Cell Activating Factor / Q000378:metabolism; D002648:Child; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D007596:Joints / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D053264:B-Cell Activating Factor; D007070:Immunoglobulin A; D020381:Interleukin-17; C505719:TNFSF13B protein, human; D053773:Transforming Growth Factor beta1
B-cell activating factor of the TNF family; Immunoglobulin A; Interleukin-17; Synovial fluid; Transforming growth factor