Department of Paediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei, Taiwan.
Rheumatology (Oxford). 2010 Jan;49(1):34-42. doi: 10.1093/rheumatology/kep328. Epub 2009 Nov 17.
Prothrombin (PT) is one of the most important antigenic targets for aPL antibodies; however, the prothrombotic mechanism of anti-PT (aPT) antibodies in APS is not fully clarified. Considering that some autoantibodies possess the enzymatic activity, the aim of this study was to test the hypothesis that some aPT antibodies in APS may display prothrombinase activity.
Six APS patient-derived PT-reactive monoclonal antibodies (mAbs) were analysed for prothrombinase activity on PT. One mAb with prothrombinase activity was examined for its proteolytic activity on PT. In addition, IgG was purified from plasma samples positive with IgG aPT antibodies, and their prothrombinase activity analysed.
Initial analysis of six mAbs revealed that, upon incubation with PT, IS6 mAb displayed prothrombinase activity and catalysed the proteolysis of PT to fragments. Analysis of plasma samples revealed that 9/21 (42.8%) APS patients had IgG antibodies against PT, based on a cut-off value equal to mean + 3 S.D. of the level in 21 normal controls. Importantly, of those samples positive for IgG aPT antibodies, two polyclonal IgG (P1 and P2) also displayed prothrombinase activity.
In this study, we showed that some aPT antibodies displayed prothrombinase activity. Such catalytic aPT antibodies may contribute to thrombosis in APS.
凝血酶原（PT）是抗磷脂抗体（aPL 抗体）的最重要的抗原性靶标之一；然而，APS 中抗 PT（aPT）抗体的促血栓形成机制尚未完全阐明。鉴于一些自身抗体具有酶活性，本研究旨在检验以下假说，即 APS 中的一些 aPT 抗体可能具有凝血酶原酶活性。
分析了 6 种 APS 患者来源的 PT 反应性单克隆抗体（mAb）在 PT 上的凝血酶原酶活性。对具有凝血酶原酶活性的 1 种 mAb 进行了 PT 蛋白水解活性的检测。此外，从 IgG 抗 aPT 抗体阳性的血浆样本中纯化 IgG，并分析其凝血酶原酶活性。
初步分析 6 种 mAb 发现，在与 PT 孵育时，IS6 mAb 显示出凝血酶原酶活性，并催化 PT 水解为片段。分析血浆样本发现，21 名正常对照者的平均+3SD 作为截断值，基于该截断值，9/21（42.8%）APS 患者具有针对 PT 的 IgG 抗体。重要的是，在 IgG aPT 抗体阳性的这些样本中，2 种多克隆 IgG（P1 和 P2）也显示出凝血酶原酶活性。
在这项研究中，我们表明一些 aPT 抗体显示出凝血酶原酶活性。这种催化性 aPT 抗体可能有助于 APS 中的血栓形成。
