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The purpose of this study was to examine the predictive significance of key cytokines for long\u2010term progression of ILD and survival in 2 independent cohorts of patients with early SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma levels of 11 Th1\/Th2 cytokines (interleukin\u20101\u03b2 [IL\u20101\u03b2], IL\u20105, IL\u20106, IL\u20108, IL\u201010, IL\u201012, IL\u201013, tumor necrosis factor, CCL2, interferon\u2010inducible T cell \u03b1 chemoattractant, and interferon\u2010\u03b3\u2013inducible 10\u2010kd protein) were measured in 266 patients with early SSc in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) discovery cohort. Levels of CCL2, IL\u201010, and IL\u20106 were measured in 171 patients with early SSc in the Canadian Scleroderma Research Group (CSRG) replication cohort. The primary outcome measure was a decline in the forced vital capacity percent predicted (FVC%) value over time. A joint analysis of longitudinal FVC% values and survival was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After adjustment for age, sex, and ethnicity, CCL2 and IL\u201010 were found to be significant predictors of ILD progression in the discovery cohort. Higher CCL2 levels predicted a faster decline in FVC% values (b\u2009=\u2009\u22120.57, <jats:italic>P<\/jats:italic>\u2009=\u20090.032), while higher IL\u201010 levels predicted a slower decline (b\u2009=\u20090.26, <jats:italic>P<\/jats:italic>\u2009=\u20090.01). A higher CCL2 value was also predictive of poorer survival (hazard ratio 1.76, <jats:italic>P<\/jats:italic>\u2009=\u20090.030). In the CSRG replication cohort, higher CCL2 levels predicted a faster decline in FVC% values (b\u2009=\u2009\u22120.58, <jats:italic>P<\/jats:italic>\u2009=\u20090.038), but neither IL\u201010 nor IL\u20106 had predictive significance. A higher CCL2 level also predicted poorer survival (hazard ratio 3.89, <jats:italic>P<\/jats:italic>\u2009=\u20090.037).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Higher CCL2 levels in the circulation were predictive of ILD progression and poorer survival in patients with early SSc, findings that support the notion that CCL2 has a role as a biomarker and potential therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40171","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T12:46:44Z","timestamp":1496407604000},"page":"1871-1878","source":"Crossref","is-referenced-by-count":83,"title":["CCL2 in the Circulation Predicts Long\u2010Term Progression of Interstitial Lung Disease in Patients With Early Systemic Sclerosis: Data From Two Independent Cohorts"],"prefix":"10.1002","volume":"69","author":[{"given":"Minghua","family":"Wu","sequence":"first","affiliation":[{"name":"McGovern Medical School, University of 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