{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:56:10Z","timestamp":1790222170730,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009248","name":"Innovatiefonds Zorgverzekeraars","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009248","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"Objective<\/jats:title>Juvenile dermatomyositis (DM<\/jats:styled-content>) is a heterogeneous systemic immune\u2010mediated vasculopathy. This study was undertaken to 1) identify inflammation\/endothelial dysfunction\u2013related biomarker profiles reflecting disease severity at diagnosis, and 2) establish whether such biomarker profiles could be used for predicting the response to treatment in patients with juvenile DM<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>In total, 39 biomarkers related to activation of endothelial cells, endothelial dysfunction, and inflammation were measured using multiplex technology in serum samples from treatment\u2010naive patients with juvenile DM<\/jats:styled-content> from 2 independent cohorts (n = 30 and n = 29). Data were analyzed by unsupervised hierarchical clustering, nonparametric tests with correction for multiple comparisons, and Kaplan\u2010Meier tests with Cox proportional hazards models for analysis of treatment duration. Myositis\u2010specific antibodies (MSA<\/jats:styled-content>s) were measured in the patients\u2019 serum using line blot assays.<\/jats:p><\/jats:sec>Results<\/jats:title>Severe vasculopathy in patients with juvenile DM<\/jats:styled-content> was associated with low serum levels of intercellular adhesion molecule 1 (Spearman's rho [rs<\/jats:sub>] = 0.465, P<\/jats:italic> = 0.0111) and high serum levels of endoglin (rs<\/jats:sub> = \u22120.67, P<\/jats:italic> < 0.0001). In the discovery cohort, unsupervised hierarchical clustering analysis of the biomarker profiles yielded 2 distinct patient clusters, of which the smaller cluster (cluster 1; n = 8) exhibited high serum levels of CXCL<\/jats:styled-content>13, CCL<\/jats:styled-content>19, galectin\u20109, CXCL<\/jats:styled-content>10, tumor necrosis factor receptor type II<\/jats:styled-content> (TNFR<\/jats:styled-content>II), and galectin\u20101 (false discovery rate <0.0001), and this cluster had greater severity of muscle disease and global disease activity (each P<\/jats:italic> < 0.05 versus cluster 2). In the validation cohort, correlations between the serum levels of galectin\u20109, CXCL<\/jats:styled-content>10, TNFR<\/jats:styled-content>II, and galectin\u20101 and the severity of global disease activity were confirmed (rs<\/jats:sub> = 0.40\u20130.52, P<\/jats:italic> < 0.05). Stratification of patients according to the 4 confirmed biomarkers identified a cluster of patients with severe symptoms (comprising 64.7% of patients) who were considered at high risk of requiring more intensive treatment in the first 3 months after diagnosis (P<\/jats:italic> = 0.0437 versus other cluster). Moreover, high serum levels of galectin\u20109, CXCL<\/jats:styled-content>10, and TNFR<\/jats:styled-content>II were predictive of a longer total treatment duration (P<\/jats:italic> < 0.05). The biomarker\u2010based clusters were not evidently correlated with patients\u2019 MSA<\/jats:styled-content> serotypes.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Results of this study confirm the heterogeneity of new\u2010onset juvenile DM<\/jats:styled-content> based on serum biomarker profiles. Patients with high serum levels of galectin\u20109, CXCL<\/jats:styled-content>10, TNFR<\/jats:styled-content>II, and galectin\u20101 may respond suboptimally to conventional treatment, and may therefore benefit from more intensive monitoring and\/or treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41236","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T02:29:26Z","timestamp":1582770566000},"page":"1214-1226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Endothelial and Inflammation Biomarker Profiles at Diagnosis Reflecting Clinical Heterogeneity and Serving as a Prognostic Tool for Treatment Response in Two Independent Cohorts of Patients With Juvenile Dermatomyositis"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3835-6374","authenticated-orcid":false,"given":"Judith","family":"Wienke","sequence":"first","affiliation":[{"name":"University Medical Center Utrecht and Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Pachman","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, and the Cure JM Center of Excellence Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle A.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, and the Cure JM Center of Excellence Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Guan","family":"Yeo","sequence":"additional","affiliation":[{"name":"KK Women's and Children's Hospital, and Duke\u2010NUS Medical School Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Amoruso","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, and the Cure JM Center of Excellence Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Hans","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, and the Cure JM Center of Excellence Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia S. M.","family":"Kamphuis","sequence":"additional","affiliation":[{"name":"Sophia Children's Hospital and Erasmus University Medical Centre Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther P. A. H.","family":"Hoppenreijs","sequence":"additional","affiliation":[{"name":"Amalia Children's Hospital and Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wineke","family":"Armbrust","sequence":"additional","affiliation":[{"name":"Beatrix Children's Hospital and University Medical Centre Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Merlijn","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital and Amsterdam University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra C. E.","family":"Hissink Muller","sequence":"additional","affiliation":[{"name":"Sophia Children's Hospital and Erasmus University Medical Centre, Rotterdam, The Netherlands, and Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyra A.","family":"Gelderman","sequence":"additional","affiliation":[{"name":"Sanquin Diagnostic Services Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaschawee","family":"Arkachaisri","sequence":"additional","affiliation":[{"name":"KK Women's and Children's Hospital, and Duke\u2010NUS Medical School Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"van Wijk","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht and Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet","family":"van 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