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The predominant subtypes, oligoarticular and polyarticular JIA, are traditionally considered to be autoimmune diseases with a central role for T cells and autoantibodies. Mounting evidence suggests an important role for neutrophils in JIA pathogenesis. We undertook this study to investigate the phenotypic features of neutrophils present in the blood and inflamed joints of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>JIA synovial fluid (SF) and parallel blood samples from JIA patients and healthy children were collected. SF\u2010treated neutrophils from healthy donors and pleural neutrophils from patients with pleural effusion were investigated as controls for SF exposure and extravasation. Multicolor flow cytometry panels allowed for in\u2010depth phenotypic analysis of neutrophils, focusing on the expression of adhesion molecules, activation, and maturation markers and chemoattractant receptors. Multiplex technology was used to quantify cytokines in plasma and SF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SF neutrophils displayed an activated, hypersegmented phenotype with decreased CD62L expression, up\u2010regulation of adhesion molecules CD66b, CD11b, and CD15, and down\u2010regulation of CXCR1\/2. An elevated percentage of CXCR4\u2010positive neutrophils was detected in SF from patients. Pleural neutrophils showed less pronounced maturation differences. Strikingly, significant percentages of SF neutrophils showed a profound up\u2010regulation of atypical neutrophil markers, including CXCR3, intercellular adhesion molecule 1, and HLA\u2013DR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data show that neutrophils in inflamed joints of JIA patients have an activated phenotype. This detailed molecular analysis supports the notion that a complex intertwining between these innate immune cells and adaptive immune events drives JIA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41605","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T18:01:17Z","timestamp":1606932077000},"page":"875-884","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Synovial Fluid Neutrophils From Patients With Juvenile Idiopathic Arthritis Display a Hyperactivated Phenotype"],"prefix":"10.1002","volume":"73","author":[{"given":"Mieke","family":"Metzemaekers","sequence":"first","affiliation":[{"name":"Katholieke University Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Malengier\u2010Devlies","sequence":"additional","affiliation":[{"name":"Katholieke University Leuven  Leuven 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