Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura
Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura
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DOI：
10.1111/bjh.12004
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发表时间：
2012-10-01
影响因子：
6.5
通讯作者：
de Laat, Bas
中科院分区：
文献类型：
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作者：
Du, Vivian X.;van Os, Gwen;de Laat, Bas
研究表明，β 2-糖蛋白 I (β 2GPI) 在糖蛋白 (GP)Ib 结合状态下与冯维勒布兰德因子 (VWF) 相互作用。鉴于血栓性血小板减少性紫癜 (TTP) 中存在活性 VWF 多聚体，我们推测 β2GPI 可能在 TTP 中发挥作用。我们发现，急性和缓解期 TTP 患者的 β2GPI 血浆水平显着低于正常对照，这与 ADAMTS 13 水平呈正相关，与 VWF 激活程度呈负相关。体外流动实验表明，β2GPI 可以阻断血小板与内皮细胞衍生的 VWF 线的粘附。我们通过表面等离子共振证实了β2GPI与VWF的直接结合，并确定β2GPI的结构域I是VWF A1结构域的结合位点。在活性 VWF 存在的情况下，β 2GPI 对红细胞和血小板的粘附增加，表明在 TTP 发作期间，β 2GPI 可能与血细胞一起从循环中清除。我们的研究结果表明，β2GPI 可以通过抑制 VWF 与血小板的相互作用来防止功能亢进的 VWF 的影响。
It has been shown that beta 2-glycoprotein I (beta 2GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that beta 2GPI might play a role in TTP. We found that beta 2GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that beta 2GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of beta 2GPI to VWF by surface plasmon resonance, and determined that domain I of beta 2GPI is the binding site of VWF A1 domain. Adhesion of beta 2GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that beta 2GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that beta 2GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.