The Vasculopathy of Juvenile Dermatomyositis: Endothelial Injury, Hypercoagulability, and Increased Arterial Stiffness
Open Access
- 4 January 2021
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatology
- Vol. 73 (7), 1253-1266
- https://doi.org/10.1002/art.41639
Abstract
Objectives Vasculopathy is considered central to the pathogenesis of Juvenile dermatomyositis (JDM) and is associated with severe extra‐muscular manifestations. We hypothesised that we can non‐invasively track the vasculopathy of JDM by examining biomarkers of endothelial injury, subclinical inflammation, hypercoagulability, and vascular arterial stiffness in a UK cohort of children with JDM. Methods Circulating endothelial cells (CEC) and microparticles (MP) were identified using immunomagnetic bead extraction, and flow cytometry, respectively. Plasma thrombin generation was determined using a fluorogenic assay. Cytokines/chemokines were measured by electrochemiluminescence. Arterial stiffness was assessed using pulse wave velocity (PWV). Results were expressed as median (interquartile range), and compared with non‐parametric analyses (significance at P3/ml; compared to controls 44.3 (15.0‐249.1) x103/ml, p<0.0001. MP were predominantly of platelet and endothelial origin. Enhanced plasma thrombin generation was demonstrated in active JDM compared to inactive disease (p=0.03); and controls (p=0.001). JDM patients had increased carotid‐radial PWV adjusted for age compared to controls (p=0.005). Conclusion We observed increased endothelial injury in active JDM, and increased proinflammatory cytokines. MP profiles reflected distinct disease activity status in JDM, and are markers of vascular pathology, platelet activation and thrombotic propensity. Ongoing long‐term vascular injury may result in increased arterial stiffness in JDM.Funding Information
- F. Hoffmann-La Roche
- Swedish Orphan Biovitrum
- Pfizer
- Novartis
- Eli Lilly and Company
- Versus Arthritis
This publication has 59 references indexed in Scilit:
- Endothelial injury in childhood stroke with cerebral arteriopathyNeurology, 2012
- The PRINTO criteria for clinically inactive disease in juvenile dermatomyositisAnnals Of The Rheumatic Diseases, 2012
- Risk of Subsequent Coronary Heart Disease in Patients Hospitalized for Immune-Mediated Diseases: A Nationwide Follow-Up Study from SwedenPLOS ONE, 2012
- Clinical Status and Cardiovascular Risk Profile of Adults with a History of Juvenile DermatomyositisThe Journal of Pediatrics, 2011
- Direct thrombin inhibitorsBritish Journal of Clinical Pharmacology, 2011
- A national registry for juvenile dermatomyositis and other paediatric idiopathic inflammatory myopathies: 10 years' experience; the Juvenile Dermatomyositis National (UK and Ireland) Cohort Biomarker Study and Repository for Idiopathic Inflammatory MyopathiesRheumatology, 2010
- Validation of manual muscle testing and a subset of eight muscles for adult and juvenile idiopathic inflammatory myopathiesArthritis Care & Research, 2010
- Small vessel vasculitisPediatric Nephrology, 2009
- Late‐onset gastrointestinal pain in juvenile dermatomyositis as a manifestation of ischemic ulceration from chronic endarteropathyArthritis Care & Research, 2007
- Renal angiography in children with polyarteritis nodosaPediatric Nephrology, 2002