The Vasculopathy of Juvenile Dermatomyositis: endothelial injury, hypercoagulability, and increased arterial stiffness.

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 P<0.05). RESULTS Ninety JDM patients were included; age 10.21 (6.68-13.40) years; disease duration 1.63 (0.28-4.66) years. CEC were higher in all JDM patients at 96 (40-192) cells/ml, compared to 12 (8-24) cells/ml in 79 controls, p<0.0001. Circulating MPs were also significantly higher in active JDM: 204.7 (87.9-412.6) x103 /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.