The Vasculopathy of Juvenile Dermatomyositis: Endothelial Injury, Hypercoagulability, and Increased Arterial Stiffness.

Abstract

Vasculopathy is considered central to the pathogenesis of juvenile dermatomyositis (DM) and is associated with severe extramuscular manifestations. We undertook this study to investigate the hypothesis that the vasculopathy of juvenile DM can be noninvasively tracked by examining biomarkers of endothelial injury, subclinical inflammation, hypercoagulability, and vascular arterial stiffness. The study population was a UK cohort of children with juvenile DM. Circulating endothelial cells (CECs) and microparticles (MPs) were identified using immunomagnetic bead extraction and flow cytometry, respectively. Plasma thrombin generation was determined using a fluorogenic assay. Cytokine and chemokine levels were measured by electrochemiluminescence. Arterial stiffness was assessed using pulse wave velocity (PWV). Results were expressed as the median and interquartile range (IQR), and statistical significance was assessed using nonparametric analyses. Ninety patients with juvenile DM and 79 healthy control subjects were included. The median age of the patients was 10.21 years (IQR 6.68-13.40), and the median disease duration was 1.63 years (IQR 0.28-4.66). CEC counts were higher in all patients with juvenile DM compared to controls (median 96 cells/ml [IQR (40-192] and 12 cells/ml [IQR 8-24], respectively; P < 0.0001). Circulating MP numbers were also significantly higher in patients with active juvenile DM compared to controls (median 204.7 × 10³ /ml [IQR 87.9-412.6] and 44.3 × 10³ /ml [IQR 15.0-249.1], respectively; P < 0.0001). MPs were predominantly of platelet and endothelial origin. Enhanced plasma thrombin generation was demonstrated in patients with active juvenile DM compared to those with inactive disease (P = 0.0003) and controls (P < 0.0001). Carotid-radial PWV adjusted for age was increased in patients with juvenile DM compared to controls (P = 0.003). We observed increased endothelial injury and increased levels of proinflammatory cytokines in patients with active juvenile DM. MP profiles reflected distinct disease activity status in juvenile DM and are markers of vascular pathology, platelet activation, and thrombotic propensity. Ongoing long-term vascular injury may result in increased arterial stiffness in patients with juvenile DM.