Antibodies against the Activated Coagulation Factor X (FXa) in the Antiphospholipid Syndrome That Interfere with the FXa Inactivation by Antithrombin1
Antibodies against the Activated Coagulation Factor X (FXa) in the Antiphospholipid Syndrome That Interfere with the FXa Inactivation by Antithrombin1
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DOI：
10.4049/jimmunol.177.11.8219
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发表时间：
2006-12
期刊：
影响因子：
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通讯作者：
Yao-Hsu Yang;K. Hwang;J. Fitzgerald;J. Grossman;Mihaela B. Taylor;B. Hahn;Pojen P. Chen
中科院分区：
文献类型：
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作者：
Yao-Hsu Yang;K. Hwang;J. Fitzgerald;J. Grossman;Mihaela B. Taylor;B. Hahn;Pojen P. Chen
在抗磷脂综合征（APS）中，抗磷脂抗体已被证明可促进血栓形成和胎儿丢失。以前，我们在一些APS患者中发现IgG抗凝血酶Ab可以干扰抗凝血酶（AT）对凝血酶的灭活。考虑到活化的凝血因子X（FXa）在催化结构域中与凝血酶同源，并且也主要受AT调节，我们假设一些凝血酶反应性Ab可能与FXa结合并干扰FXa的AT失活。为了验证这些假设，我们研究了8种患者源性单克隆IgG抗磷脂抗体与FXa的反应性以及APS患者中IgG抗FXa抗体的存在，并研究了FXa反应性mAb对FXa AT失活的影响。结果表明，6种凝血酶反应性IgG mAb中有6种与FXa结合，38例APS患者血浆IgG抗FXa Ab水平显著高于30例正常对照组（P < 0.001）。以30例正常对照组的平均值加3个标准差作为临界值时，38例APS患者中有5例（13.2%）有IgG抗FXa Ab。重要的是，六种FXa反应性mAb中的三种显著抑制FXa的AT失活。总之，这些结果表明，抗FXa抗体可能通过干扰某些APS患者中AT对FXa的抗凝功能而导致血栓形成。
Antiphospholipid Ab have been shown to promote thrombosis and fetal loss in the antiphospholipid syndrome (APS). Previously, we found IgG anti-thrombin Ab in some APS patients that could interfere with inactivation of thrombin by antithrombin (AT). Considering that activated coagulation factor X (FXa) is homologous to thrombin in the catalytic domains and is also regulated primarily by AT, we hypothesized that some thrombin-reactive Ab may bind to FXa and interfere with AT inactivation of FXa. To test these hypotheses, we studied reactivity of eight patient-derived monoclonal IgG antiphospholipid Ab with FXa and the presence of IgG anti-FXa Ab in APS patients and investigated the effects of FXa-reactive mAb on AT inactivation of FXa. The results revealed that six of six thrombin-reactive IgG mAb bound to FXa and that the levels of plasma IgG anti-FXa Ab in 38 APS patients were significantly higher than those in 30 normal controls (p < 0.001). When the mean plus 3 SDs of the 30 normal controls was used as the cutoff, 5 of 38 APS patients (13.2%) had IgG anti-FXa Ab. Importantly, three of six FXa-reactive mAb significantly inhibited AT inactivation of FXa. Combined, these results indicate that anti-FXa Ab may contribute to thrombosis by interfering with the anticoagulant function of AT on FXa in some APS patients.