Mechanisms of vascular injury and dysfunction in pediatric lupus
Pediatric-onset lupus is often more severe than adult-onset lupus. This puts kids with lupus at a higher risk of having heart attacks and strokes when they are young adults. We do not yet know how to monitor this damage as it occurs, much less how to prevent it. With her grant from the Lupus Research Alliance, Dr. Chang will conduct a long-term study of teens with lupus to monitor, over time, their blood pressure patterns along with DNA shed by immune cells in their blood. She hopes to find a marker that will measure early blood vessel injury, so patients with increased risk of cardiovascular trouble later in life can be identified, watched, and appropriately treated.
What this study means for people with lupus
Some children with lupus are at risk of heart disease as they grow up. Dr. Chang aims to devise a non-invasive test using specific markers to help predict their future risk, so they can be monitored and treated before damage occurs.
Pediatric-onset systemic lupus erythematosus (pSLE) carries a high risk of premature cardiovascular disease, but responsive surrogate measures of cardiovascular risk for pediatric patients are currently lacking. Neutrophil extracellular traps (NETs) have recently been implicated in the pathogenesis of both SLE and atherosclerosis via endothelial activation in vitro, however nothing is known about NET-mediated endothelial injury and dysfunction in children and adolescents with pSLE. Endothelial dysfunction precedes structural changes in the continuum of atherosclerosis and may be a more sensitive, early indicator of vascular injury. This project is a longitudinal study of adolescents with pSLE recruited to undergo measurement of plasma NET levels and comprehensive vascular testing, including peripheral endothelial function testing and ambulatory blood pressure monitoring to assess nocturnal blood pressure decline, a potential surrogate marker of endothelial function. The objectives of this proposal are to: 1) determine the effect of pSLE and clinical disease activity measures on plasma NET levels, 2) determine the in vivo relationship between NET levels, markers of endothelial activation, and peripheral endothelial function in pSLE, and 3) determine whether NBP decline, a novel surrogate marker of atherosclerotic risk, is independently associated with peripheral endothelial function and structural evidence of subclinical atherosclerosis in adolescents with pSLE. The long-term goal is to understand mechanisms of vascular injury in pSLE and identify clinically useful biomarkers for earlier, more effective CV risk stratification and outcome assessment. Dr. Chang completed a Master of Science in Clinical Epidemiology at the University of Pennsylvania and has additional research training in non-invasive measures of cardiovascular health in pSLE. She was recently hired as an Assistant Professor at the Children’s Hospital of Philadelphia for clinical research and utilizes an interdisciplinary approach to accelerate advances in cardiorheumatology with an emphasis on pSLE. The proposed research will contribute to our understanding of immunologic mechanisms of vascular injury and dysfunction in SLE, and apply novel, non-invasive approaches to cardiovascular assessment in children and adolescents with SLE.