Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulants and other "antiphospholipid" autoantibodies.
Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulants and other "antiphospholipid" autoantibodies.
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DOI：
10.1182/blood.v84.9.2854.bloodjournal8492854
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发表时间：
1994-11
期刊：
影响因子：
20.3
通讯作者：
R. Roubey
中科院分区：
文献类型：
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作者：
R. Roubey
抗凝血剂和一般的“抗磷脂”自身抗体具有相当重要的临床意义，因为它们与血栓形成、复发性流产和血小板减少症（即“抗磷脂”抗体综合征）密切相关。这篇评论集中在最近的证据表明，“抗磷脂”自身抗体不针对阴离子磷脂，如以前所认为的，但对某些磷脂结合血浆蛋白的自身抗体的一个更大的群体的一部分。目前，最常见和最好表征的抗原靶点是I（P2 GPI β ′-*）和prothr~mbin。其他磷脂结合蛋白，特别是蛋白C和蛋白S，也可能是重要的靶点。具有这些特异性的自身抗体不同于获得性凝血因子抑制剂，因为它们优先结合固定在阴离子磷脂膜或某些合成表面上的抗原。在大多数情况下，抗体与液相中的抗原的结合是弱的或不可检测的。因此，这种自身抗体通常不降低血浆抗原水平。虽然缺乏“抗磷脂”自身抗体的病理生理学作用的直接证据，但据推测，磷脂结合蛋白的自身抗体通过干扰体内阴离子磷脂膜上发生的止血反应而直接导致血栓形成素质。有趣的是，自身抗体对靶抗原功能的影响可能会有所不同。例如，P2 GPI的某些抗体增强其活性，而磷脂结合的活化蛋白C的抗体是抑制性的。总的来说，这些新的观察结果解释了许多关于用于检测“抗磷脂”抗体的实验室测试的混乱，并为“抗磷脂”抗体综合征的病理生理学提供了关键的见解。
L UPUS ANTICOAGULANTS, and “antiphospholipid” autoantibodies in general, are of considerable clinical importance because of their strong association with thrombosis, recurrent fetal loss, and thrombocytopenia, ie, the “antiphospholipid” antibody syndrome.’ This review focuses on recent evidence that “antiphospholipid” autoantibodies are not directed against anionic phospholipids, as has previously been thought, but are part of a larger group of autoantibodies against certain phospholipid-binding plasma proteins. At present, the most common and best characterized antigenic targets are I (P2GPI)’-* and prothr~mbin.~”~ Other phospholipid-binding proteins, particularly protein C and protein S,” may be important targets as well. Autoantibodies with these specificities differ from acquired coagulation factor inhibitors in that they preferentially bind antigens that are immobilized on anionic phospholipid membranes or certain synthetic surfaces. In most instances, antibody binding to the antigens in the fluid-phase is weak or nondetectable. Thus, such autoantibodies usually do not decrease plasma antigen levels. Although direct evidence for a pathophysiologic role of “antiphospholipid” autoantibodies is lacking, it is hypothesized that autoantibodies to phospholipid-binding proteins contribute directly to a thrombotic diathesis by interfering with hemostatic reactions that occur on anionic phospholipid membranes in vivo. Interestingly, the effect of autoantibodies on target antigen function may vary. For example, certain antibodies to P2GPI enhance its activity,””’ whereas antibodies to phospholipid-bound activated protein C are inhibitory.” Taken together, these new observations explain much of the confusion regarding the laboratory tests used to detect “ antiphospholipid” antibodies and are providing key insights into the pathophysiology of the “antiphospholipid” antibody syndrome.