Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome
Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome
复制标题
DOI：
10.1182/blood-2004-01-0203
复制
发表时间：
2004-11-01
期刊：
影响因子：
20.3
通讯作者：
Ortel, TL
中科院分区：
文献类型：
--
作者：
Rand, JH;Wu, XX;Ortel, TL
膜联蛋白A5（A5）在磷脂双层上形成二维晶体，阻止其用于凝血反应。最近，人抗磷脂（aPL）单克隆抗体（mAb）已被证明通过原子力显微镜（AFM），以破坏这种结晶和加速凝固。因此，我们进行了一项研究，与小，明确的患者群体，以调查是否这些影响A5的结合和活性也可检测到血浆中的aPL综合征患者。与健康对照组相比，aPL综合征和血栓栓塞患者血浆中A5与磷脂的结合显著降低（平均值+/- SD，26.7 +/- 4.3 ng/孔[n = 25] vs 30.5 +/- 3.1 ng/孔[n = 20]，P <0.01）和非aPL血栓栓塞组（29.9 +/- 3.2 ng/孔[n = 15]，P <0.05）。与无血栓形成的aPL抗体相比，aPL综合征和血栓栓塞患者的血浆A5抗凝活性降低（182 31% [n = 25] vs 210 +/- 35% [n = 26]，P < .01），非aPL血栓栓塞（229 +/- 16% [n = 15]，P <0.001）和健康对照组（231 +/- 14% [n = 30]，P <0.001）。总之，根据最近的AFM数据与单克隆人aPL抗体，血浆与aPL抗体与血栓栓塞患者减少：A5结合磷脂和A5抗凝活性。这种“膜联蛋白A5抗性”确定了aPL综合征中血栓形成的新机制。(C)2004年，美国血液学会。
Annexin A5 (A5) forms 2-dimensional crystals over phospholipid bilayers, blocking their availability for coagulation reactions. Recently, human antiphospholipid (aPL) monoclonal antibodies (mAbs) have been demonstrated by atomic force microscopy (AFM) to disrupt this crystallization and accelerate coagulation. We therefore performed a study with small, well-defined groups of patients to investigate whether these effects on A5 binding and activity are also detectable in plasmas from patients with the aPL syndrome. A5 binding to phospholipid was significantly reduced by plasmas of patients with the aPL syndrome and thromboembolism compared with healthy controls (mean +/- SD, 26.7 +/- 4.3 ng/well [n = 25] vs 30.5 +/- 3.1 ng/well [n = 20], P < .01) and the non-aPL thromboembolism group (29.9 +/- 3.2 ng/well [n = 15], P < .05). A5 anticoagulant activity was reduced by plasmas of patients with aPL syndrome and thromboembolism compared with aPL antibodies without thrombosis (182 31% [n = 25] vs 210 +/- 35% [n = 26], P < .01), non-aPL thromboembolism (229 +/- 16% [n = 15], P < .001), and healthy controls (231 +/- 14% [n = 30], P < .001). In conclusion, in accordance with recent AFM data with monoclonal human aPL antibodies, plasmas from patients with aPL antibodies with thromboembolism reduce: both A5 binding to phospholipid and A5 anticoagulant activity. This "annexin A5 resistance" identifies a novel mechanism for thrombosis in the aPL syndrome. (C) 2004 by The American Society of Hematology.