Children's Hospital at Montefiore, Department of Pediatrics, Division of Rheumatology, Bronx, NY 10467, USA.
J Rheumatol. 2012 Feb;39(2):382-8. doi: 10.3899/jrheum.110768. Epub 2011 Dec 15.
The underlying mechanism(s) by which antiphospholipid antibodies (aPL) result in thrombosis remains poorly understood. A significant body of evidence has evolved to support the hypothesis that antibody-mediated disruption of an annexin A5 anticoagulant shield may play a role in the pathogenesis; this proposed mechanism has not been previously studied in children.
We investigated the association between aPL and resistance to annexin A5 anticoagulant activity in 90 children with a variety of rheumatic diseases using a novel mechanistic assay, the annexin A5 resistance assay (A5R).
Patients with a diagnosis of primary aPL syndrome, systemic lupus erythematosus, and mixed connective tissue disease demonstrated lower mean A5R levels (p = 0.030), higher prevalence of positive aPL (p < 0.001), and more thrombotic events (p = 0.014) compared to those with other diagnoses. Patients with persistently positive aPL had significantly lower mean A5R compared to patients with no aPL (mean A5R = 203% ± 44% vs 247% ± 35%; p < 0.001), whereas patients with transient aPL did not. Patients with thrombosis had lower A5R levels compared to those without thrombosis (mean A5R = 207% ± 36% vs 237% ± 46%; p = 0.048).
Children and adolescents with rheumatic diseases and persistent aPL have reduced annexin A5 anticoagulant activity, whereas transient, nonpathogenic aPL have less effect on annexin A5 activity.
抗磷脂抗体 (aPL) 导致血栓形成的潜在机制仍知之甚少。大量证据支持抗体介导的破坏 annexin A5 抗凝屏蔽可能在发病机制中起作用的假说；这一提出的机制以前尚未在儿童中进行过研究。
我们使用一种新的机制性测定法，即 annexin A5 抵抗测定法 (A5R)，研究了 90 名患有各种风湿性疾病的儿童中 aPL 与 annexin A5 抗凝活性抵抗之间的关联。
与其他诊断相比，原发性 aPL 综合征、系统性红斑狼疮和混合性结缔组织病患者的平均 A5R 水平较低（p = 0.030），aPL 阳性率较高（p < 0.001），血栓事件更多（p = 0.014）。与无 aPL 的患者相比，持续存在 aPL 的患者的平均 A5R 明显较低（平均 A5R = 203% ± 44%比 247% ± 35%；p < 0.001），而一过性 aPL 的患者则不然。与无血栓形成的患者相比，发生血栓形成的患者的 A5R 水平较低（平均 A5R = 207% ± 36%比 237% ± 46%；p = 0.048）。
患有风湿性疾病和持续性 aPL 的儿童和青少年 annexin A5 抗凝活性降低，而短暂性、非致病性 aPL 对 annexin A5 活性的影响较小。
