Shi W, Chong B H, Chesterman C N
Department of Haematology, Prince of Wales Hospital, School of Pathology, University of New South Wales, Sydney, Australia.
Blood. 1993 Mar 1;81(5):1255-62.
Antiphospholipid (aPL) antibodies are of major interest not only because the lupus anticoagulant (LA) causes an inhibition of in vitro blood coagulation, but also because the presence of aPL antibodies confers a risk of thrombosis. The inhibition of in vitro phospholipid-dependent coagulation (LA) is thought to be caused by the binding of LA to procoagulant phospholipid surfaces, thus impeding the clotting process. Another class of aPL antibodies are those originally described to be directed against negatively charged phospholipids, in particular cardiolipin (ACA). ACA are usually directed against a complex antigen consisting of negatively charged phospholipid and a plasma protein, beta 2-glycoprotein I (beta 2-GPI). Further, there is antibody heterogeneity even within individual patients so that ACA and LA are separable using physicochemical techniques such as ion exchange chromatography and chromatofocusing. Using such techniques we have enriched Ig fractions for LA and ACA from two patient plasmas. The majority of Ig with LA activity had a pI of 7.2 to 7.3 whereas ACA had a pI of 5.0 to 5.2. Using these enriched fractions labeled with [125I]-iodine we have shown that LA binds to platelets in a specific and saturable manner. Binding is dependent on thrombin activation. [125I]-ACA behaves differently. Like LA, binding is specific and dependent on thrombin activation but in this case requires the presence of beta 2-GPI. ACA, in the presence of beta 2-GPI, competes for binding with LA suggesting the same or contiguous site. There is no cross-reactivity of these antibodies with GPIIb/IIIa and the most likely binding site is phospholipid. In neither case does LA nor ACA have an effect on thrombin-induced release of serotonin or beta-thromboglobulin nor do they affect platelet aggregation induced by a number of agonists. This antibody binding may play an etiological role in thrombocytopenia associated with aPL, but does not explain thrombosis on the basis of hyperaggregability or increased platelet release.
抗磷脂（aPL）抗体备受关注，不仅因为狼疮抗凝物（LA）会抑制体外血液凝固，还因为aPL抗体的存在会带来血栓形成风险。体外磷脂依赖性凝血的抑制作用（LA）被认为是由LA与促凝磷脂表面结合引起的，从而阻碍了凝血过程。另一类aPL抗体是最初被描述为针对带负电荷磷脂的抗体，特别是心磷脂（ACA）。ACA通常针对由带负电荷磷脂和血浆蛋白β2-糖蛋白I（β2-GPI）组成的复合抗原。此外，即使在个体患者中也存在抗体异质性，因此可以使用离子交换色谱和聚焦色谱等物理化学技术将ACA和LA分离。利用这些技术，我们从两名患者血浆中富集了LA和ACA的Ig组分。大多数具有LA活性的Ig的pI为7.2至7.3，而ACA的pI为5.0至5.2。使用这些用[125I] -碘标记的富集组分，我们已经表明LA以特异性和可饱和的方式与血小板结合。结合依赖于凝血酶激活。[125I] -ACA的行为不同。与LA一样，结合是特异性的且依赖于凝血酶激活，但在这种情况下需要β2-GPI的存在。在β2-GPI存在的情况下，ACA与LA竞争结合，表明存在相同或相邻的位点。这些抗体与GPIIb/IIIa没有交叉反应，最可能的结合位点是磷脂。在这两种情况下，LA和ACA都不会对凝血酶诱导的5-羟色胺或β-血小板球蛋白释放产生影响，也不会影响多种激动剂诱导的血小板聚集。这种抗体结合可能在与aPL相关的血小板减少症中起病因学作用，但不能基于血小板过度聚集或血小板释放增加来解释血栓形成。
