Correlation between the potency of a beta2-glycoprotein I-dependent lupus anticoagulant and the level of resistance to activated protein C

被引:35
作者
de Laat, Bas [1 ,2 ]
Eckmann, Carel M. [1 ]
van Schagen, Marlies [1 ]
Meijer, Alexander B. [2 ]
Mertens, Koen [2 ,3 ]
van Mourik, Jan A. [1 ,2 ,4 ]
机构
[1] Diagnost Serv Sanquin, Dept Blood Coagulat, Amsterdam, Netherlands
[2] Sanquin Res, Dept Plasma Prot, Amsterdam, Netherlands
[3] Univ Utrecht, UIPS, Dept Pharmaceut, Utrecht, Netherlands
[4] Amsterdam Med Ctr, Dept Vasc Med, Amsterdam, Netherlands
关键词
anti phospholipid; beta(2)-glycoprotein I; factor V Leiden; protein C;
D O I
10.1097/MBC.0b013e32830f1b85
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The anti phospholipid syndrome is characterized by the occurrence of vascular thrombosis combined with the presence of antiphospholipid antibodies in plasma of patients. It has been published that antibeta2-glycoprotein I (beta(2)-GPI) antibodies, with lupus anticoagulant activity (LAC), highly correlate with thrombosis. Resistance related to antiphospholipid antibodies against activated protein C (APC) is one of the proposed mechanisms responsible for thrombosis. We investigated a possible correlation between a beta(2)-GPI-dependent LAC (titration of cardiolipin into an activated partial thromboplastin time-based assay) and increased APC resistance in a population of 22 plasma samples with LAC activity. Eleven plasma samples that displayed a beta(2)-GPI-dependent LAC also showed increased APC resistance. In contrast, only one of the 11 plasma samples with a beta(2)-GPI-independent LAC displayed increased APC resistance. In addition, a monoclonal antibeta(2)-GPI antibody and patient-purified immunoglobulin G (both with LAC activity) were diluted in plasma with/without protein C. Both antibodies only displayed a beta(2)-GPI-dependent LAC in plasma in the presence of protein C. This indicates that the principle of the beta(2)-GPI LAC-assay was based on increased resistance against protein C. Surface plasmon resonance analysis was used to investigate binding between APC and beta(2)-GPI. We observed that beta(2)-GPI was able to bind APC directly, especially in the presence of a monoclonal aritibeta(2)-GPI antibody. In conclusion, our observations show a direct correlation between a major clinical symptom of antiphospholipid syndrome (thrombosis), a diagnostic assay (beta(2)-GPI-dependent LAC) and a potential mechanism responsible for thrombosis in the antiphospholipid syndrome (increased APC resistance). Blood Coagul Fibrinolysis 19:757 - 764 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:757 / 764
页数:8
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