Centre for Rheumatology, Division of Medicine University College London, Rayne Institute, 4 th Floor, Room 422, 5 University Street, London.
Thromb Haemost. 2013 Jan;109(1):72-8. doi: 10.1160/TH12-05-0346. Epub 2012 Nov 15.
IgG antiphospholipid antibodies (aPL) exert direct effects on various cell types, contributing to the pathogenesis of thrombosis and pregnancy morbidity in patients with the antiphospholipid syndrome (APS). Some IgG samples from these patients activate endothelial cells (EC) in vitro as judged by surface expression of adhesion molecules such as E-selectin, which can promote thrombosis. Endothelial microparticles (EMP), which themselves are potentially prothrombotic, are released by activated EC. Though elevated circulating EMP levels have been reported in patients with APS, it is not known whether these EMP are released due to a direct effect of aPL on the cells. We tested the effect of purified polyclonal IgG from patients with APS (APS-IgG) and healthy controls (HC-IgG) upon cultured human umbilical vein EC (HUVEC). HUVEC exposed to APS-IgG produced significantly more EMP than those exposed to HC-IgG (p=0.0036) and a greater proportion of these EMP carried surface E-selectin (6.2% ± 4.0 for APS-IgG vs. 3.4% ± 2.0 for HC IgG, p=0.0172). This study therefore demonstrates that purified polyclonal APS-IgG can drive EMP release. We propose that EMP generation may be a useful measure of aPL-mediated pathogenic effects upon EC.
IgG 抗磷脂抗体 (aPL) 对各种细胞类型发挥直接作用，导致抗磷脂综合征 (APS) 患者的血栓形成和妊娠发病率增加。从这些患者中提取的一些 IgG 样本通过表面表达粘附分子（如 E-选择素）在体外激活内皮细胞 (EC)，这有助于促进血栓形成。被激活的 EC 释放自身具有潜在促血栓形成的内皮微粒 (EMP)。尽管已经报道 APS 患者的循环中 EMP 水平升高，但尚不清楚这些 EMP 是否由于 aPL 对细胞的直接作用而释放。我们测试了来自 APS 患者的纯化多克隆 IgG (APS-IgG) 和健康对照 (HC-IgG) 对培养的人脐静脉内皮细胞 (HUVEC) 的影响。暴露于 APS-IgG 的 HUVEC 产生的 EMP 明显多于暴露于 HC-IgG 的 HUVEC (p=0.0036)，并且这些 EMP 中有更大比例携带表面 E-选择素 (APS-IgG 为 6.2%±4.0，HC IgG 为 3.4%±2.0，p=0.0172)。因此，本研究表明纯化的多克隆 APS-IgG 可驱动 EMP 释放。我们提出，EMP 的产生可能是衡量 aPL 对 EC 产生致病性影响的有用指标。
