{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:19:52Z","timestamp":1779189592529,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,10,27]],"date-time":"2012-10-27T00:00:00Z","timestamp":1351296000000},"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":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic juvenile idiopathic arthritis (JIA) is an autoinflammatory syndrome in which the myelomonocytic lineage appears to play a pivotal role. Inflammatory macrophages are driven by interferon\u2010\u03b3 (IFN\u03b3), but studies have failed to demonstrate an IFN\u2010 induced gene signature in active systemic JIA. This study sought to characterize the status of an IFN\u2010induced signature within affected tissue and to gauge the integrity of IFN signaling pathways within peripheral monocytes from patients with systemic JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synovial tissue from 12 patients with active systemic JIA and 9 with active extended oligoarticular JIA was assessed by real\u2010time polymerase chain reaction to quantify IFN\u2010induced chemokine gene expression. Peripheral monocytes from 3 patients with inactive systemic JIA receiving anti\u2013interleukin\u20101\u03b2 (anti\u2013IL\u20101\u03b2) therapy, 5 patients with active systemic JIA, and 8 healthy controls were incubated with or without IFN\u03b3 to gauge changes in gene expression and to measure phosphorylated STAT\u20101 (pSTAT\u20101) levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IFN\u2010induced chemokine gene expression in synovium was constrained in active systemic JIA compared to the known IFN\u2010mediated extended oligoarticular subtype. In unstimulated peripheral monocytes, IFN\u2010induced gene expression was similar between the groups, except that lower levels of STAT1, MIG, and PIAS were observed in patients with active disease, while higher levels of PIAS1 were observed in patients with inactive disease. Basal pSTAT\u20101 levels in monocytes tended to be higher in systemic JIA patients compared to healthy controls, with the highest levels seen in those with inactive disease. Upon stimulation of monocytes, the fold increase in gene expression was roughly equal between groups, except for a greater increase in STAT1 in patients with inactive systemic JIA compared to controls, and a greater increase in IRF1 in those with active compared to inactive disease. Upon stimulation, the fold increase in pSTAT\u20101 was highest in monocytes from patients with inactive systemic JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Monocytes in patients with active systemic JIA retain the ability to respond to IFN\u03b3, suggesting that the lack of an IFN\u2010induced gene signature in patients with active disease reflects a limited in vivo exposure to IFN\u03b3. In patients with inactive systemic JIA who received treatment with anti\u2013IL\u20101\u03b2, hyperresponsiveness to IFN\u03b3 was observed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34604","type":"journal-article","created":{"date-parts":[[2012,6,27]],"date-time":"2012-06-27T19:48:45Z","timestamp":1340826525000},"page":"3799-3808","source":"Crossref","is-referenced-by-count":45,"title":["The limited role of interferon\u2010\u03b3 in systemic juvenile idiopathic arthritis cannot be explained by cellular hyporesponsiveness"],"prefix":"10.1002","volume":"64","author":[{"given":"Keith A.","family":"Sikora","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ndate","family":"Fall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry","family":"Thornton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexei 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