Dignat-George Françoise, Camoin-Jau Laurence, Sabatier Florence, Arnoux Dominique, Anfosso Francine, Bardin Nathalie, Veit Véronique, Combes Valéry, Gentile Stéphanie, Moal Valérie, Sanmarco Marielle, Sampol José
INSERM EMI 0019: Physiopathology of the endothelium, UFR de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France.
Thromb Haemost. 2004 Apr;91(4):667-73. doi: 10.1160/TH03-07-0487.
The antiphospholipid syndrome (APS) refers to persistent anti-phospholipid antibodies (aPL) associated with thrombotic and/or obstetrical complications. The endothelial cell is a target of aPL which can induce a procoagulant and proinflammatory endothelial phenotype, as reported both in vivo and in vitro. Microparticle production is a hallmark of cell activation. In the present study, the presence of endothelial microparticles (EMP) in the plasma of APS patients was investigated. To determine if there is a correlation with certain biological and clinical features, EMP levels were measured in thrombosis-free patients with systemic lupus erythematosus (SLE) patients, with and without aPL, in patients with non aPL-related thrombosis, as well as in healthy controls. Compared to healthy subjects, elevated plasma levels of EMP were found in patients with APS and in SLE patients with aPL, but not in SLE patients without aPL or in non aPL-related thrombosis. EMP levels were also associated with Lupus Anticoagulant (LA) detected by a positive Dilute Russell's Viper Venom time (DRVVT). In parallel, we analyzed the capacity of these plasma to induce vesiculation of cultured endothelial cells. We demonstrated an increase of EMP generated in response to plasma from patients with auto-immune diseases. Interestingly, only APS plasma induced the release of EMP with procoagulant activity. These ex vivo and in vitro observations indicate that generation of EMP in APS and SLE patients results from an autoimmune process involving aPL. Production of procoagulant microparticles in APS patients may represent a new pathogenic mechanism for the thrombotic complications of this disease.
抗磷脂综合征（APS）是指与血栓形成和/或产科并发症相关的持续性抗磷脂抗体（aPL）。内皮细胞是aPL的靶标，体内和体外研究均表明，aPL可诱导促凝血和促炎的内皮细胞表型。微粒产生是细胞活化的标志。在本研究中，我们调查了APS患者血浆中内皮微粒（EMP）的存在情况。为了确定其是否与某些生物学和临床特征相关，我们检测了无血栓形成的系统性红斑狼疮（SLE）患者（有或无aPL）、非aPL相关血栓形成患者以及健康对照者的EMP水平。与健康受试者相比，APS患者和有aPL的SLE患者血浆中EMP水平升高，而无aPL的SLE患者或非aPL相关血栓形成患者则未升高。EMP水平还与通过稀释蝰蛇毒时间（DRVVT）阳性检测到的狼疮抗凝物（LA）相关。同时，我们分析了这些血浆诱导培养内皮细胞形成囊泡的能力。我们发现，自身免疫性疾病患者血浆刺激产生的EMP增加。有趣的是，只有APS患者的血浆能诱导具有促凝血活性的EMP释放。这些体内外观察结果表明，APS和SLE患者体内EMP的产生是一个涉及aPL的自身免疫过程。APS患者促凝血微粒的产生可能是该疾病血栓形成并发症的一种新的致病机制。
