George J, Blank M, Levy Y, Meroni P, Damianovich M, Tincani A, Shoenfeld Y
Department of Medicine B Sheba Medical Center, Tel Hashomer, Israel.
Circulation. 1998 Mar 10;97(9):900-6. doi: 10.1161/01.cir.97.9.900.
The antiphospholipid syndrome (APS) entails a prothrombotic state associated with the presence of anticardiolipin antibodies (aCL). aCL were shown to promote endothelial cell and platelet activation and to induce an APS-like syndrome in mice when administered intravenously. Recent data suggest that aCL target the plasma cofactor beta2-glycoprotein I (beta2GPI) rather than negatively charged phospholipids. However, it has not been determined whether different epitope-specific anti-beta2GPI antibodies obtained from one patient possess pathogenic properties.
Three beta2GPI-binding IgM monoclonal antibodies (mAbs) (ILA-1, ILA-3, and ILA-4) were cloned from a patient with APS. The three antibodies were shown to bind beta2GPI immobilized on irradiated plates, yet only ILA-1 bound beta2GPI coated onto nonirradiated plates. Furthermore, when using the anti-beta2GPI enzyme-linked immunosorbent assay, ILA-1 was the only mAb inhibited by fluid phase beta2GPI. ILA-1 and ILA-3, but not ILA-4, induced adherence of U937 cells to endothelial cells in vitro (reflecting activation of endothelial cells). mAbs ILA-1 and ILA-3 as opposed to ILA-4 induced significant expression of adhesion molecules when preincubated with human umbilical vein endothelial cells. Passive administration of ILA-1 and ILA-3 to pregnant BALB/c mice induced clinical findings consistent with APS (increased fetal resorptions, reduced platelet counts, and prolonged activated partial thromboplastin time), whereas both ILA-4 and the control human IgM did not produce similar effects.
The results of the study demonstrate the differential effects of various populations of anti-beta2GPI antibodies on endothelial cell activation and on experimental APS.
抗磷脂综合征（APS）是一种与抗心磷脂抗体（aCL）存在相关的血栓前状态。静脉注射aCL可促进内皮细胞和血小板活化，并在小鼠中诱导出类似APS的综合征。最近的数据表明，aCL靶向血浆辅因子β2-糖蛋白I（β2GPI）而非带负电荷的磷脂。然而，尚未确定从一名患者获得的不同表位特异性抗β2GPI抗体是否具有致病特性。
从一名APS患者中克隆出三种β2GPI结合IgM单克隆抗体（mAb）（ILA-1、ILA-3和ILA-4）。这三种抗体均能结合固定在辐照板上的β2GPI，但只有ILA-1能结合包被在未辐照板上的β2GPI。此外，在使用抗β2GPI酶联免疫吸附测定时，ILA-1是唯一受液相β2GPI抑制的mAb。ILA-1和ILA-3（而非ILA-4）在体外诱导U937细胞与内皮细胞黏附（反映内皮细胞活化）。与ILA-4相反，mAb ILA-1和ILA-3在与人脐静脉内皮细胞预孵育时诱导黏附分子显著表达。将ILA-１和ILA-3被动给予怀孕的BALB/c小鼠可诱导出与APS一致的临床表现（胎儿吸收增加、血小板计数减少和活化部分凝血活酶时间延长），而ILA-4和对照人IgM均未产生类似效果。
该研究结果表明不同群体的抗β2GPI抗体对内皮细胞活化和实验性APS具有不同作用。
