Erdbruegger U, Grossheim M, Hertel B, Wyss K, Kirsch T, Woywodt A, Haller H, Haubitz M
Division of Nephrology, Department of Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Rheumatology (Oxford). 2008 Dec;47(12):1820-5. doi: 10.1093/rheumatology/ken373. Epub 2008 Oct 16.
Endothelial cells play a central pathogenetic role in ANCA-associated small-vessel vasculitis (AAV). Circulating endothelial cells (CECs), as a marker of endothelial damage, have been shown to be elevated in vasculitis. More recently, endothelial microparticles (EMPs) were found to be increased in active childhood vasculitis. The role of EMP in adult AAV and the relationship between EMP and CEC is unclear.
We studied 26 patients with AAV, 12 healthy volunteers and 10 patients with IgA nephropathy as disease control. Platelet-poor plasma was ultracentrifuged. MPs were identified and enumerated with flow cytometry, Annexin V, CD62E and CD105 antibodies. Leucocyte- and platelet-derived MPs were also measured. CEC were isolated and enumerated with CD146-driven immuno-magnetic isolation.
EMPs are significantly elevated in patients with active vasculitis (CD62E: mean 248 MP/microl +/- 198 s.d.; CD105: 121 +/- 135/microl) compared with patients in remission/partial remission (CD62E: 55 +/- 30/microl, P = 0.001; CD105: 16 +/- 12/microl, P = 0.002) and healthy volunteers (CD62E: 66 +/- 33/microl, P = 0.002; CD105: 25 +/- 26/microl, P = 0.007). The MP count correlates with disease activity measured by the Birmingham Vasculitis Activity Score (BVAS) (CD62E: r = 0.703; CD105: r = 0.445, P < 0.023).
EMPs are elevated in active adult AAV. EMP levels correlate with disease activity and might serve as a marker of endothelial activation and damage. Differential detection of endothelial, platelet- and leucocyte-derived MPs may provide more insight in to the pathogenesis of AAV.
内皮细胞在抗中性粒细胞胞浆抗体相关性小血管炎(AAV)中起核心致病作用。循环内皮细胞(CEC)作为内皮损伤的标志物,已证实在血管炎中升高。最近发现,内皮微粒(EMP)在儿童活动性血管炎中增加。EMP在成人AAV中的作用以及EMP与CEC之间的关系尚不清楚。
我们研究了26例AAV患者、12名健康志愿者以及10例IgA肾病患者作为疾病对照。对乏血小板血浆进行超速离心。用流式细胞术、膜联蛋白V、CD62E和CD105抗体鉴定并计数微粒。还检测了白细胞和血小板衍生的微粒。通过CD146驱动的免疫磁珠分离法分离并计数CEC。
与缓解期/部分缓解期患者(CD62E:平均55±30个微粒/微升,P = 0.001;CD105:16±12个微粒/微升,P = 0.002)和健康志愿者(CD62E:66±33个微粒/微升,P = 0.002;CD105:25±26个微粒/微升,P = 0.007)相比,活动性血管炎患者的EMP显著升高(CD62E:平均248个微粒/微升±198标准差;CD105:121±135个微粒/微升)。微粒计数与通过伯明翰血管炎活动评分(BVAS)测量的疾病活动度相关(CD62E:r = 0.703;CD105:r = 0.445,P < 0.023)。
活动性成人AAV中EMP升高。EMP水平与疾病活动度相关,可能作为内皮激活和损伤的标志物。内皮、血小板和白细胞衍生微粒的差异检测可能为AAV的发病机制提供更多见解。