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- W4313351570 abstract "Abstract The early events leading to the development of rheumatoid arthritis remain unclear but formation of autoantibodies to citrullinated antigens is considered a key pathogenic phenomenon. Neutrophils isolated from patients with various autoimmune diseases display enhanced extracellular trap formation, a phenomenon that externalizes autoantigens and immunostimulatory molecules. We investigated if aberrant NETosis occurs in RA, its triggers and deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and synovial fluid RA neutrophils. NETosis correlated with ACPA levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. During NETosis, neutrophils externalized citrullinated autoantigens implicated in RA pathogenesis, while anti-citrullinated vimentin antibodies potently induced NET formation. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant immune responses in the joint and in the periphery and perpetuate pathogenic mechanisms in this disease." @default.
- W4313351570 created "2023-01-06" @default.
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- W4313351570 date "2013-05-01" @default.
- W4313351570 modified "2023-09-23" @default.
- W4313351570 title "Neutrophil extracellular traps are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis (P4061)" @default.
- W4313351570 doi "https://doi.org/10.4049/jimmunol.190.supp.127.2" @default.
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