{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:03:21Z","timestamp":1792782201769,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Institut Roche"},{"name":"Association des Scl\u00e9rodermies de France"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"\n Objective<\/jats:title>\n \n Interstitial lung disease (\n ILD<\/jats:styled-content>\n ) in systemic sclerosis (\n SS<\/jats:styled-content>\n c) runs a highly variable course, and prediction tools are highly desired. The aim of this study was to assess the diagnostic and prognostic performance of 4 candidate serum biomarkers for\n SS<\/jats:styled-content>\n c\u2010associated\n ILD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Serum samples from a combined cohort of\n SS<\/jats:styled-content>\n c patients (from Paris, France and Oslo, Norway; n = 427) were analyzed by enzyme\u2010linked immunosorbent assay for concentrations of lung epithelial\u2013derived surfactant protein D (\n SP<\/jats:styled-content>\n \u2010D), Krebs von den Lungen 6 glycoprotein (\n KL<\/jats:styled-content>\n \u20106),\n CCL<\/jats:styled-content>\n 18, and\n OX<\/jats:styled-content>\n 40 ligand (\n OX<\/jats:styled-content>\n 40L). Lung fibrosis was measured by high\u2010resolution computed tomography and pulmonary function tests. Associations of these candidate biomarkers with baseline disease involvement and prediction of disease progression over time (mean \u00b1\n SD<\/jats:styled-content>\n follow\u2010up 3.2 \u00b1 4.4 years) were investigated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In\n SS<\/jats:styled-content>\n c patients at baseline, serum levels of\n KL<\/jats:styled-content>\n \u20106 correlated with the forced vital capacity (\n FVC<\/jats:styled-content>\n ) (r = \u22120.317,\n P<\/jats:italic>\n < 0.001), diffusing capacity for carbon monoxide (r = \u22120.335,\n P<\/jats:italic>\n < 0.001), and extent of lung fibrosis (r = 0.551,\n P<\/jats:italic>\n < 0.001). In multivariate analyses, serum levels of\n KL<\/jats:styled-content>\n \u20106 and\n SP<\/jats:styled-content>\n \u2010D, but not\n CCL<\/jats:styled-content>\n 18 and\n OX<\/jats:styled-content>\n 40L, were associated with lung fibrosis (odds ratio [\n OR<\/jats:styled-content>\n ] 2.41, 95% confidence interval [95%\n CI<\/jats:styled-content>\n ] 1.43\u20134.07 [\n P<\/jats:italic>\n = 0.001] and\n OR<\/jats:styled-content>\n 3.15, 95%\n CI<\/jats:styled-content>\n 1.81\u20135.48 [\n P<\/jats:italic>\n < 0.001], respectively). In\n SS<\/jats:styled-content>\n c patients with\n ILD<\/jats:styled-content>\n at baseline, longitudinal, multivariate analyses showed that\n CCL<\/jats:styled-content>\n 18 serum levels were an independent predictor of a >10% decrease in the\n FVC<\/jats:styled-content>\n (hazard ratio [\n HR<\/jats:styled-content>\n ] 2.90, 95%\n CI<\/jats:styled-content>\n 1.25\u20136.73;\n P<\/jats:italic>\n = 0.014) and de novo development of extensive disease (\n HR<\/jats:styled-content>\n 3.71, 95%\n CI<\/jats:styled-content>\n 1.02\u201313.52;\n P<\/jats:italic>\n = 0.048). Matrix\u2010based logistic regression models for the diagnosis and prognosis of\n SS<\/jats:styled-content>\n c\u2010associated\n ILD<\/jats:styled-content>\n were constructed, and these models discriminated 3 groups of risk (mild, moderate, or high) for the diagnosis or worsening of lung fibrosis according to the serum levels of\n SP<\/jats:styled-content>\n \u2010D (for diagnosis) and serum levels of\n CCL<\/jats:styled-content>\n 18 (for progression of disease).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These results show that\n SP<\/jats:styled-content>\n \u2010D is a relevant diagnostic biomarker for\n SS<\/jats:styled-content>\n c\u2010associated\n ILD<\/jats:styled-content>\n , whereas\n KL<\/jats:styled-content>\n \u20106 could be used to assess the severity of lung fibrosis.\n CCL<\/jats:styled-content>\n 18 appears to be a potential predictive marker for progression of\n ILD<\/jats:styled-content>\n in\n SS<\/jats:styled-content>\n c.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.40815","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T06:45:00Z","timestamp":1547016300000},"page":"972-982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["Performance of Candidate Serum Biomarkers for Systemic Sclerosis\u2013Associated Interstitial Lung Disease"],"prefix":"10.1002","volume":"71","author":[{"given":"Muriel","family":"Elhai","sequence":"first","affiliation":[{"name":"INSERM U1016, UMR8104, Cochin Institute, Paris Descartes University, and Cochin Hospital, Paris Descartes University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Hoffmann\u2010Vold","sequence":"additional","affiliation":[{"name":"Oslo University Hospital, Oslo and Institute of Clinical Medicine University of Oslo Oslo 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