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

• Published in: BMC immunology Vol. 18; no. 1; p. 8
• Main Authors: Eliçabe, Ricardo Javier, Silva, Juan Eduardo, Dave, Mabel Noemí, Lacoste, María Gabriela, Tamashiro, Héctor, Blas, Rodrigo, Munarriz, Alicia, Rabinovich, Gabriel Adrián, Di Genaro, María Silvia
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06-02-2017; BioMed Central
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigens; Arthritis; B-Cell Activating Factor - metabolism; BLyS protein; Child; Cytokines; Disease; Enterobacteriaceae Infections - immunology; Enzyme-linked immunosorbent assay; Enzymes; Female; Health aspects; Helper cells; Humans; Immunodiffusion; Immunoglobulin A; Immunoglobulin A - metabolism; Immunoglobulins; Inflammation - immunology; Inflammatory bowel disease; Inflammatory diseases; Interleukin 17; Interleukin 6; Interleukin-17 - immunology; Interleukin-17 - metabolism; Interleukins; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Joint diseases; Joints - immunology; Leukocytes (mononuclear); Lipopolysaccharides; Lymphocytes B; Lymphocytes T; Male; Middle Aged; Mucosa; Osteoarthritis; Physiological aspects; Rheumatic diseases; Rheumatoid arthritis; Spondylitis, Ankylosing - immunology; Synovial fluid; Th17 Cells - immunology; Transforming Growth Factor beta1 - immunology; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b; Transforming growth factor-b1; Tumor necrosis factor; Variance analysis; Young Adult; United States > US; Argentina; Synovial fluid; B-cell activating factor of the TNF family; Interleukin-17; Immunoglobulin A; Transforming growth factor
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-017-0189-9

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