IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis

• Published in: Frontiers in immunology 2021-10, Vol.12, p.745523
• Main Authors: Navrátilová, Adela, Andrés Cerezo, Lucie, Hulejová, Hana, Bečvář, Viktor, Tomčík, Michal, Komarc, Martin, Veigl, David, Tegzová, Dana, Závada, Jakub, Olejárová, Marta, Pavelka, Karel, Vencovský, Jiří, Šenolt, Ladislav
• Format: Article
• Language: English
• Subjects: Adalimumab - therapeutic use; Adult; Aged; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - therapy; autoantibodies; Autoantibodies - blood; B cells; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biomarkers; Cells, Cultured; Cohort Studies; Cytokines - analysis; disease activity; Extracellular Traps - immunology; Female; Fibroblasts; Gene Expression Regulation - drug effects; Humans; Immunology; interleukin-40; Interleukins - metabolism; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lymphocyte Depletion; Male; Matrix Metalloproteinase 13 - analysis; Middle Aged; NETosis; Osteoarthritis, Knee - immunology; Osteoarthritis, Knee - metabolism; rheumatoid arthritis; Rituximab - pharmacology; Rituximab - therapeutic use; Synovial Fluid - chemistry; Synovial Fluid - immunology; Synovial Membrane - chemistry; Synovial Membrane - immunology; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.745523

Interleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA). IL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined. IL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p