Bordron A, Dueymes M, Levy Y, Jamin C, Leroy J P, Piette J C, Shoenfeld Y, Youinou P Y
Laboratory of Immunology, "Institut de Synergie des Sciences et de la Santé," Brest University Medical School, F 29 609 Brest, France.
J Clin Invest. 1998 May 15;101(10):2029-35. doi: 10.1172/JCI2261.
The pathogenic role of antiendothelial cell antibodies (AECA) remains unclear. They are frequently associated with antibodies to anionic phospholipids (PL), such as phosphatidylserine (PS), which is difficult to reconcile with the distribution of PL molecular species within the plasma membrane. Since it is already known that PS is transferred to the outer face of the membrane as a preclude to apoptosis, the possibility exists that apoptosis is initiated by AECA. AECA-positive/anti-PL antibody-negative sera from eight patients with systemic sclerosis (SS) and 21 control patients were evaluated. Endothelial cells (EC) were incubated with AECA and the exposure of PS was established through the binding of annexin V. Hypoploid cell enumeration, DNA fragmentation, and optical and ultrastructural analyses of EC were used to confirm apoptosis. Incubation of EC with AECA derived from six of eight patients with SS led to the expression of PS on the surface of the cells. This phenomenon was significantly more frequent in SS (P < 0.04) than in control diseases. The redistribution of plasma membrane PS preceded other events associated with apoptosis: hypoploidy, DNA fragmentation, and morphology characteristic for apoptosis. Apoptosis-inducing AECA did not recognize the Fas receptor. We conclude that AECA may be pathogenic by inducing apoptosis.
抗内皮细胞抗体（AECA）的致病作用仍不明确。它们常与抗阴离子磷脂（PL）抗体相关，如磷脂酰丝氨酸（PS），这难以与细胞膜内PL分子种类的分布相协调。由于已知PS作为细胞凋亡的前奏会转移到膜的外表面，因此存在AECA引发细胞凋亡的可能性。对8例系统性硬化症（SS）患者和21例对照患者的AECA阳性/抗PL抗体阴性血清进行了评估。将内皮细胞（EC）与AECA一起孵育，并通过膜联蛋白V的结合来确定PS的暴露情况。使用EC的亚二倍体细胞计数、DNA片段化以及光学和超微结构分析来确认细胞凋亡。用8例SS患者中6例患者的AECA孵育EC导致细胞表面PS的表达。这种现象在SS患者中比在对照疾病中明显更常见（P < 0.04）。质膜PS的重新分布先于与细胞凋亡相关的其他事件：亚二倍体、DNA片段化以及细胞凋亡的形态特征。诱导细胞凋亡的AECA不识别Fas受体。我们得出结论，AECA可能通过诱导细胞凋亡而致病。
