{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T09:56:04Z","timestamp":1785318964207,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,7,30]],"date-time":"2009-07-30T00:00:00Z","timestamp":1248912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Accumulation of apoptotic cells may lead to the development of systemic lupus erythematosus (SLE) through a breakdown in immune tolerance. Altered neutrophil apoptosis may contribute to nuclear autoantigen exposure, ultimately leading to autoantibody generation. This study aimed to determine whether neutrophil apoptosis is altered in patients with juvenile\u2010onset SLE as compared with controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Apoptosis was measured in neutrophils from patients with juvenile\u2010onset SLE (n = 12), adult\u2010onset SLE (n = 6), and pediatric patients with inflammatory (n = 12) and noninflammatory (n = 12) conditions. Annexin V staining and flow cytometry were used to determine neutrophil apoptosis. Proapoptotic and antiapoptotic proteins were measured in sera and in neutrophil cell lysates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Neutrophil apoptosis was significantly increased in patients with juvenile\u2010onset SLE as compared with the noninflammatory controls at time 0. Incubation of neutrophils with sera from patients with juvenile\u2010onset SLE further increased neutrophil apoptosis as compared with incubation with sera from pediatric controls. Concentrations of TRAIL and FasL were significantly increased in sera from patients with juvenile\u2010onset SLE, whereas interleukin\u20106, tumor necrosis factor \u03b1, and granulocyte\u2013macrophage colony\u2010stimulating factor (GM\u2010CSF) were significantly decreased. Addition of GM\u2010CSF to sera from patients with juvenile\u2010onset SLE significantly decreased neutrophil apoptosis as compared with juvenile\u2010onset SLE sera alone. The expression of proapoptotic proteins (caspase 3, Fas, and FADD) was elevated in juvenile\u2010onset SLE neutrophils, whereas the expression of antiapoptotic proteins (cellular inhibitor of apoptosis 1 and 2 and X\u2010linked inhibitor of apoptosis) was decreased. Neutrophil apoptosis correlated with biomarkers of disease activity (erythrocyte sedimentation rate and double\u2010stranded DNA concentration) and the British Isles Lupus Assessment Group disease activity score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data demonstrate an imbalance in proapoptotic and antiapoptotic factors in both neutrophils and sera from patients with juvenile\u2010onset SLE. This imbalance results in increased neutrophil apoptosis in these patients. Correlations with markers of disease activity indicate that altered neutrophil apoptosis in juvenile\u2010onset SLE patients may play a pathogenic role in this condition.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24634","type":"journal-article","created":{"date-parts":[[2009,7,30]],"date-time":"2009-07-30T15:15:42Z","timestamp":1248966942000},"page":"2390-2401","source":"Crossref","is-referenced-by-count":83,"title":["The role of neutrophil apoptosis in juvenile\u2010onset systemic lupus erythematosus"],"prefix":"10.1002","volume":"60","author":[{"given":"Angela","family":"Midgley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"McLaren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Moots","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven 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