β2-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model
β2-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model
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DOI：
10.1182/blood-2010-08-300715
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发表时间：
2011-03-24
期刊：
影响因子：
20.3
通讯作者：
Furie, Bruce
中科院分区：
文献类型：
--
作者：
Arad, Ariela;Proulle, Valerie;Furie, Bruce
抗磷脂综合征的特征是血栓形成、复发性流产和狼疮抗凝剂、抗心磷脂抗体或抗β 2-糖蛋白1（抗β 2-GP 1）抗体的存在。尽管抗β 2-GP 1抗体已被证明是诊断抗磷脂综合征的生物标志物，但其在血栓形成发病机制中的直接作用尚不清楚。我们用活体显微镜证实，从抗磷脂综合征并发血栓形成患者血清中纯化的抗β 2-GP 1自身抗体，在激光诱导的活小鼠血管壁损伤后，大大放大了血栓的大小。用琼脂糖结合人β（2）-GP 1亲和纯化3例抗磷脂综合征患者的抗β（2）-GP 1自身抗体。在小鼠提睾肌动脉损伤后，测定了纯化的抗β（2）GP 1 IgG自身抗体、抗β（2）-GP 1耗尽IgG和正常人血清IgG对血栓形成的影响。在损伤前，输注纯化的抗β（2）-GP 1 IgG自身抗体、抗β（2）-GP 1抗体耗尽的IgG或来自正常人血清的IgG。增加纯化的抗β（2）-GP 1自身抗体的量以剂量依赖性方式增加血栓大小，而抗β（2）-GP 1抗体耗尽的IgG或来自正常血清的IgG均不影响血栓大小。这些结果表明，抗磷脂综合征患者血清中的抗β（2）-GP 1 IgG自身抗体不仅是抗磷脂综合征的标志物，而且直接参与血栓形成的发病机制。（血。2011; 117（12）：3453-3459）
Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, and the presence of the lupus anticoagulant, anticardiolipin antibodies, or anti-beta(2)-glycoprotein-1 (anti-beta(2)-GP1) antibodies. Although anti-beta(2)-GP1 antibodies have been documented as a biomarker for diagnosis of antiphospholipid syndrome, their direct role in the pathogenesis of thrombosis is unknown. We have demonstrated using intravital microscopy that anti-beta(2)-GP1 autoantibodies purified from the sera of patients with antiphospholipid syndrome complicated by thrombosis greatly amplify thrombus size after laser-induced vessel wall injury in live mice. Anti-beta(2)-GP1 autoantibodies from 3 patients with antiphospholipid syndrome were affinity-purified using human beta(2)-GP1 bound to agarose. The effects of purified anti-beta(2)GP1 IgG autoantibodies, of anti-beta(2)-GP1-depleted IgG, and of IgG from normal human sera on thrombus formation were measured in mice after arterial injury in the cremaster muscle. Before injury, purified anti-beta(2)-GP1 IgG autoantibodies, anti-beta(2)-GP1 antibody-depleted IgG, or IgG from normal human sera were infused. Increasing amounts of purified anti-beta(2)-GP1 autoantibodies increased thrombus size in a dose-dependent manner, whereas neither anti-beta(2)-GP1 antibody-depleted IgG nor IgG from normal serum affected thrombus size. These results indicate that anti-beta(2)-GP1 IgG autoantibodies in antiphospholipid syndrome patient sera are not only a marker of antiphospholipid syndrome but are directly involved in the pathogenesis of thrombosis. (Blood. 2011; 117(12): 3453-3459)