Department of Medicine, Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA, USA.
Lupus. 2010 Apr;19(4):365-9. doi: 10.1177/0961203310361488.
The body has an elaborate system that maintains blood circulation and rapidly stops bleeding when vessels are damaged. Abnormalities that disrupt this balance may lead to thrombosis. While beta(2)-glycoprotein I is generally accepted as the major antigen for antiphospholipid antibodies in the antiphospholipid syndrome, our accumulated studies show that some antiphospholipid antibodies bind homologous enzymatic domains of several serine proteases involved in hemostasis and fibrinolysis. Functionally, some of the protease-reactive antiphospholipid antibodies hinder anticoagulant regulation and resolution of clots, thus tip the balance toward thrombosis. Intriguingly, several serine protease-reactive antiphospholipid antibodies also react with beta(2)-glycoprotein I, and interactions between antiphospholipid antibodies and antigens are cross-inhibited, indicating that these antiphospholipid antibodies recognize conformational epitope(s) on beta(2)-glycoprotein I and target serine proteases. Viewed as a whole, these results extend previous reports that antiphospholipid antibodies bind to various hemostasis factors, and provide a new perspective about some antiphospholipid antibodies in terms of their binding specificities and related functional properties in promoting thrombosis.
人体有一个复杂的系统，可以在血管受损时维持血液循环并迅速止血。当这种平衡被打破时，可能会导致血栓形成。虽然β2-糖蛋白 I 通常被认为是抗磷脂综合征中抗磷脂抗体的主要抗原，但我们的累积研究表明，一些抗磷脂抗体结合了几种参与止血和纤维蛋白溶解的丝氨酸蛋白酶的同源酶结构域。从功能上讲，一些与蛋白酶反应的抗磷脂抗体阻碍抗凝剂的调节和血栓的溶解，从而导致血栓形成的倾向。有趣的是，一些丝氨酸蛋白酶反应性抗磷脂抗体也与β2-糖蛋白 I 反应，抗磷脂抗体和抗原之间的相互作用受到交叉抑制，这表明这些抗磷脂抗体识别β2-糖蛋白 I 上的构象表位，并靶向丝氨酸蛋白酶。总的来说，这些结果扩展了以前的报告，即抗磷脂抗体结合各种止血因子，并为一些抗磷脂抗体提供了一个新的视角，即它们的结合特异性和相关的功能特性在促进血栓形成方面。
