一种与凝血酶交叉反应的抗心磷脂抗体可结合并抑制活化蛋白C的抗凝功能。
A thrombin-cross-reactive anticardiolipin antibody binds to and inhibits the anticoagulant function of activated protein C.
作者信息
Hwang Kwan-Ki, Yang Cheng-De, Yan Weihong, Grossman Jennifer M, Hahn Bevra H, Chen Pojen P
机构信息
Medicine/Rheumatology, University of California, Los Angeles, CA 90095-1670, USA.
出版信息
Arthritis Rheum. 2003 Jun;48(6):1622-30. doi: 10.1002/art.10983.
OBJECTIVE
To test the hypotheses that some thrombin-reactive anticardiolipin antibodies (aCL) may bind to protein C (PC) and/or activated PC (APC), and that some of the PC- and APC-reactive aCL may inhibit PC activation and/or the function of APC.
METHODS
We studied the reactivity of patient-derived monoclonal aCL with PC and APC. We examined the effects of the reactive antibodies on PC activation and on the activity of APC in plasma coagulation.
RESULTS
Five of 5 patient-derived, thrombin-reactive monoclonal aCL bound to PC and APC. In addition, 1 patient-derived monoclonal antiprothrombin antibody (APT) that displayed aCL activity and reacted with thrombin also bound to PC and APC. Of these 6 PC- and APC-reactive aCL/APT, all failed to inhibit PC activation, but 1 (CL15) shortened the plasma coagulation time in the presence of exogenous APC and thus inhibited the anticoagulant function of APC.
CONCLUSION
Most of the thrombin-reactive aCL in patients with antiphospholipid syndrome may bind to PC and APC. Of the APC-reactive aCL, some (like CL15) may inhibit the anticoagulant function of APC and are thus likely to be prothrombotic in the host.
目的
验证以下假设，即某些凝血酶反应性抗心磷脂抗体（aCL）可能与蛋白C（PC）和/或活化蛋白C（APC）结合，且某些与PC和APC反应的aCL可能抑制PC活化和/或APC的功能。
方法
我们研究了患者来源的单克隆aCL与PC和APC的反应性。我们检测了反应性抗体对PC活化以及血浆凝血中APC活性的影响。
结果
5例患者来源的凝血酶反应性单克隆aCL中有5例与PC和APC结合。此外，1例显示aCL活性且与凝血酶反应的患者来源的单克隆抗凝血酶原抗体（APT）也与PC和APC结合。在这6种与PC和APC反应的aCL/APT中，所有均未能抑制PC活化，但1种（CL15）在存在外源性APC的情况下缩短了血浆凝血时间，从而抑制了APC的抗凝功能。
结论
抗磷脂综合征患者中大多数凝血酶反应性aCL可能与PC和APC结合。在与APC反应的aCL中，有些（如CL15）可能抑制APC的抗凝功能，因此在宿主体内可能具有促血栓形成作用。
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