Kornberg A, Renaudineau Y, Blank M, Youinou P, Shoenfeld Y
Institute of Hematology, Assaf Harofeh Medical Center, Zerifin, Israel.
Isr Med Assoc J. 2000 Jul;2 Suppl:27-31.
Anti-beta 2-glycoprotein I antibodies bind to endothelial cells through beta 2-GPI. The antibodies are present in patients with systemic lupus erythematosus and antiphospholipid syndrome and are associated with the pathogenesis of the disease. Anti-endothelial cell antibodies that react with constitutive antigens on ECs are present in patients with vasculiditis and other diseases. Both types of antibodies can activate ECs. Frequent findings in APLS and vasculitis are fibrin deposits and thromboembolic phenomena. These indicate that the coagulation system is activated. However, the mechanism of activation is not clear. ECs generate tissue factor upon stimulation with various substances. In the present study we report that monoclonal anti-beta 2-GPI antibodies and AECAs, derived from a patient with primary APLS and a patient with Takayasu's arteritis, respectively, induce a potent tissue factor in ECs. The production of TF activity, TF antigen and TF mRNA is dose and time dependent. The TF activity was induced also by F(ab)2 but not by Fc fragments and was abolished completely by pre-incubation with ant-TF antibodies. The TF that is induced in ECs by AECAs with and without beta 2-GPI specificity may activate the coagulation and thereby play a major role in the pathogenesis of fibrin deposition and thrombus formation in diseases that are associated with the presence of these antibodies.
抗β2糖蛋白I抗体通过β2-GPI与内皮细胞结合。这些抗体存在于系统性红斑狼疮和抗磷脂综合征患者中，并与疾病的发病机制相关。与内皮细胞上组成性抗原发生反应的抗内皮细胞抗体存在于血管炎和其他疾病患者中。这两种抗体均可激活内皮细胞。抗磷脂综合征和血管炎中常见的表现是纤维蛋白沉积和血栓栓塞现象。这些表明凝血系统被激活。然而，激活机制尚不清楚。内皮细胞在受到各种物质刺激后会产生组织因子。在本研究中，我们报告分别源自一名原发性抗磷脂综合征患者和一名大动脉炎患者的单克隆抗β2-GPI抗体和抗内皮细胞抗体，可在内皮细胞中诱导产生强效组织因子。组织因子活性、组织因子抗原和组织因子mRNA的产生呈剂量和时间依赖性。F(ab)2也可诱导组织因子活性，但Fc片段则不能，并且与抗组织因子抗体预孵育可完全消除该活性。具有或不具有β2-GPI特异性的抗内皮细胞抗体在内皮细胞中诱导产生的组织因子可能激活凝血，从而在与这些抗体存在相关的疾病中纤维蛋白沉积和血栓形成的发病机制中起主要作用。
