{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:04:17Z","timestamp":1793930657226,"version":"4.8.0"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000940","name":"Arthritis Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000940","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk stratification of SSc\u2013associated interstitial lung disease (SSc\u2010ILD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed 28 biomarkers in 640 participants: 259 patients with SSc\u2010ILD and 179 SSc patients without ILD (Australian Scleroderma Cohort Study), 172 patients with idiopathic pulmonary fibrosis (IPF\u2010controls) (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. We evaluated the performance of the index to identify ILD, and specifically SSc\u2010ILD, and its association with lung function, disease extent on radiography, and patient health\u2013related quality of life in derivation and validation cohorts. Biomarkers to distinguish SSc\u2010ILD from IPF\u2010controls were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A composite biomarker index, comprising surfactant protein D (SP\u2010D), Ca15\u20103, and intercellular adhesion molecule 1 (ICAM\u20101), was strongly associated with SSc\u2010ILD diagnosis, independent of age, sex, smoking history, and lung function (for biomarker index score 3, pooled adjusted odds ratio was 12.72 (95% confidence interval 4.59\u201335.21) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). The composite index strengthened the performance of individual biomarkers for SSc\u2010ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (for biomarker index score 3 relative to biomarker index score 0, the adjusted absolute change in forced vital capacity percent predicted was \u221217.84% and the diffusing capacity for carbon monoxide percent predicted was \u221220.16%; both <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A composite serum biomarker index, comprising SP\u2010D, Ca15\u20103, and ICAM\u20101, may improve the identification and risk stratification of ILD in SSc patients at baseline.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42491","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T01:27:02Z","timestamp":1678670822000},"page":"1424-1433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A Composite Serum Biomarker Index for the Diagnosis of Systemic Sclerosis\u2013Associated Interstitial Lung Disease: A Multicenter, Observational Cohort Study"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2844-4370","authenticated-orcid":false,"given":"Adelle S.","family":"Jee","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Royal Prince Alfred Hospital, School of Medicine, University of Sydney Faculty of Medicine and Health, and Australia National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Stewart","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College, London, UK, and National Institute for Health Research Biomedical Research Centre, Respiratory Research Unit University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-3999","authenticated-orcid":false,"given":"Peter","family":"Youssef","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Sydney Faculty of Medicine and Health, and Institute of Rheumatology and Orthopaedics Royal Prince Alfred Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Adelstein","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Sydney Faculty of Medicine and Health, and Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, and Central Immunopathology Laboratory, NSW Health Pathology  New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Lai","sequence":"additional","affiliation":[{"name":"Bosch Institute, Molecular Biology Facility University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Hua","sequence":"additional","affiliation":[{"name":"Bosch Institute, Molecular Biology Facility University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Rheumatology St. Vincent's Hospital, Fitzroy  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Proudman","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Royal Adelaide Hospital, and Discipline of Medicine University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene\u2010Siew","family":"Ngian","sequence":"additional","affiliation":[{"name":"Department of Inflammatory Diseases, Monash Health, Melbourne, Victoria, Australia, and Department of Medicine, Monash University, Department of Rheumatology  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian N.","family":"Glaspole","sequence":"additional","affiliation":[{"name":"Australia National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis, Department of Medicine, Central Clinical School, Monash University, and Commercial Department of Respiratory Medicine Alfred Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuben P.","family":"Moodley","sequence":"additional","affiliation":[{"name":"NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Department of Respiratory Medicine, Fiona Stanley Hospital, and Institute for Respiratory Health University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane F.","family":"Bleasel","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, Faculty of Health Medicine and Wellbeing The University of Newcastle  Callaghan New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Macansh","sequence":"additional","affiliation":[{"name":"Lung Foundation Australia  Milton Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandana","family":"Nikpour","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, St. Vincent's Hospital Melbourne, and Department of Medicine The University of Melbourne, St. Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Sahhar","sequence":"additional","affiliation":[{"name":"Department of Inflammatory Diseases, Monash Health, Melbourne, Victoria, Australia, and Department of Medicine, Monash University, Department of Rheumatology  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamera J.","family":"Corte","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Royal Prince Alfred Hospital, School of Medicine, University of Sydney Faculty of Medicine and Health, and Australia National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Australian Scleroderma Cohort Study, Australian Scleroderma Interest Group, Australian Idiopathic Pulmonary Fibrosis Registry, and associated 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