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Arthritis Rheumatol. 2020 Feb 26. doi: 10.1002/art.41236. [Epub ahead of print]

Endothelial and inflammatory biomarker profile at diagnosis reflects clinical heterogeneity of juvenile dermatomyositis and is prognostic for response to treatment in two independent cohorts.

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Laboratory of translational immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Northwestern's Feinberg School of Medicine; Cure JM Center of Excellence in JM Care and Research.
Rheumatology and Immunology, KK Women's and Children's Hospital and Duke-NUS Medical School, Singapore, Singapore.
Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.
Paediatric Rheumatology, Sophia Children's Hospital, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Department of Paediatrics, Paediatric Rheumatology, Amalia Children's Hospital, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Department of Paediatric Rheumatology, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, The Netherlands.
Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Center (AUMC), University of Amsterdam, The Netherlands.
Department of Paediatric Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Sanquin Diagnostic Services, Amsterdam, Amsterdam, Netherlands.
Pediatric rheumatology and immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.



In juvenile dermatomyositis (JDM), a heterogeneous systemic immune-mediated vasculopathy, we aim to 1) identify inflammation/endothelial dysfunction-related biomarker profiles reflecting disease severity at diagnosis; 2) establish if biomarker profiles can predict response to treatment.


39 markers related to endothelial activation, dysfunction and inflammation were measured in treatment-naive JDM patient serum from two independent cohorts (n=30/n=29) by multiplex technology. Data were analyzed by unsupervised hierarchical clustering, non-parametric tests with correction for multiple testing, and Kaplan-Meier and cox-proportional-hazards-model for analysis of treatment duration. Myositis-specific antibodies (MSA) were measured by lineblot.


Severe vasculopathy was associated with low ICAM-1 (rs =0.465, p=0.0111) and high endoglin (rs =-0.67, p<0.0001). Unsupervised clustering of the discovery cohort with all markers yielded two distinct patient clusters: the smaller cluster (n=8), with high levels of CXCL13, CCL19, galectin-9, CXCL10, TNFR2 and galectin-1 (FDR<0.0001), had higher muscle and global disease activity (p<0.05). In the validation cohort, correlations of galectin-9, CXCL10, TNFR2 and galectin-1 with global disease activity were confirmed (rs =0.40-0.52, p<0.05). Stratification of patients by these 4 markers identified those with severe symptoms, at risk of requiring more intense treatment in the first 3 months (64.7% vs. 34.1% of patients, p=0.0437). High galectin-9, CXCL10, and TNFR2 were predictive of a longer total treatment duration (p<0.05). The biomarker-based clusters were not evidently correlated with MSA serotypes.


This study confirms the heterogeneity of new-onset JDM using serum biomarkers. Patients with high galectin-9, CXCL10, TNFR2 and galectin-1 may respond suboptimally to conventional treatment, and may benefit from more intensive monitoring and/or treatment.


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