Clarke L A, Hong Y, Eleftheriou D, Shah V, Arrigoni F, Klein N J, Brogan P A
Institute of Child Health, University College London and Great Ormond Street Hospital National Health Service Trust, London, UK.
Arthritis Rheum. 2010 Jun;62(6):1770-80. doi: 10.1002/art.27418.
Endothelial injury is central to the pathogenesis of vasculitis. The purpose of this study was to assess how indices of endothelial injury and repair change during different stages of disease activity in children with primary systemic vasculitis (PSV).
Fifty children with PSV, 17 children with nonvasculitic inflammatory diseases (pediatric inflammatory disease controls), 35 healthy age- and sex-matched pediatric controls, and 27 healthy adult controls were included in the study. Biomarkers examined were endothelial microparticles (EMPs), circulating endothelial cells (CECs), angiogenic growth factors, and endothelial progenitor cells (EPCs). EMP binding to annexin V, EMPs expressing CD144 or E-selectin, and EPCs expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34 were examined by flow cytometry. CECs were enumerated using immunomagnetic bead extraction techniques, and VEGF and angiopoietin 2 (Ang-2) were measured by enzyme-linked immunosorbent assay.
Levels of CD144+ EMPs, CECs, VEGF, and EPCs were all significantly elevated in children with active vasculitis as compared with healthy children, and the levels declined with remission-inducing therapy in the individual patients. Treatment-naive patients with active disease had significantly higher levels of VEGF and Ang-2 than did those with active disease who were receiving treatment, although the levels of CECs and EMPs remained high in both of these groups.
Elevation of the levels of CECs, EMPS, EPCs, VEGF, and Ang-2 occurs during active vasculitis in children. EPC responses to active vasculitis are different in children as compared with that observed in adults with vasculitis, and both CECs and EMPs can be used to monitor disease activity in children with vasculitis.
内皮损伤是血管炎发病机制的核心。本研究旨在评估原发性系统性血管炎（PSV）患儿疾病活动不同阶段内皮损伤和修复指标的变化情况。
本研究纳入了50例PSV患儿、17例非血管炎性炎症性疾病患儿（儿科炎症性疾病对照）、35例年龄和性别匹配的健康儿科对照以及27例健康成人对照。检测的生物标志物包括内皮微粒（EMP）、循环内皮细胞（CEC）、血管生成生长因子和内皮祖细胞（EPC）。通过流式细胞术检测EMP与膜联蛋白V的结合、表达CD144或E-选择素的EMP以及表达血管内皮生长因子受体2（VEGFR-2）、CD133和CD34的EPC。使用免疫磁珠提取技术计数CEC，并通过酶联免疫吸附测定法测量VEGF和血管生成素2（Ang-2）。
与健康儿童相比，活动性血管炎患儿的CD144⁺ EMP、CEC、VEGF和EPC水平均显著升高，且个体患者的这些水平随诱导缓解治疗而下降。未经治疗的活动性疾病患者的VEGF和Ang-水平显著高于接受治疗的活动性疾病患者，尽管这两组的CEC和EMP水平均保持较高。
儿童活动性血管炎期间CEC、EMPS、EPC、VEGF和Ang-2水平升高。与成人血管炎患者相比，儿童对活动性血管炎的EPC反应有所不同，CEC和EMP均可用于监测儿童血管炎的疾病活动。
