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• W3007738892 abstract "Objective Juvenile dermatomyositis ( DM ) is a heterogeneous systemic immune‐mediated vasculopathy. This study was undertaken to 1) identify inflammation/endothelial dysfunction–related 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 . Methods In total, 39 biomarkers related to activation of endothelial cells, endothelial dysfunction, and inflammation were measured using multiplex technology in serum samples from treatment‐naive patients with juvenile DM 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‐Meier tests with Cox proportional hazards models for analysis of treatment duration. Myositis‐specific antibodies ( MSA s) were measured in the patients’ serum using line blot assays. Results Severe vasculopathy in patients with juvenile DM was associated with low serum levels of intercellular adhesion molecule 1 (Spearman's rho [r s ] = 0.465, P = 0.0111) and high serum levels of endoglin (r s = −0.67, P < 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 13, CCL 19, galectin‐9, CXCL 10, tumor necrosis factor receptor type II ( TNFR II), and galectin‐1 (false discovery rate <0.0001), and this cluster had greater severity of muscle disease and global disease activity (each P < 0.05 versus cluster 2). In the validation cohort, correlations between the serum levels of galectin‐9, CXCL 10, TNFR II, and galectin‐1 and the severity of global disease activity were confirmed (r s = 0.40–0.52, P < 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 = 0.0437 versus other cluster). Moreover, high serum levels of galectin‐9, CXCL 10, and TNFR II were predictive of a longer total treatment duration ( P < 0.05). The biomarker‐based clusters were not evidently correlated with patients’ MSA serotypes. Conclusion Results of this study confirm the heterogeneity of new‐onset juvenile DM based on serum biomarker profiles. Patients with high serum levels of galectin‐9, CXCL 10, TNFR II, and galectin‐1 may respond suboptimally to conventional treatment, and may therefore benefit from more intensive monitoring and/or treatment." @default.
• W3007738892 created "2020-03-06" @default.
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• W3007738892 date "2020-05-29" @default.
• W3007738892 modified "2023-10-18" @default.
• W3007738892 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" @default.
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• W3007738892 doi "https://doi.org/10.1002/art.41236" @default.
• W3007738892 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7329617" @default.
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