Differential effects of anti-beta(2)-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome

Article

关键词: ANTICARDIOLIPIN ANTIBODIES;    RECOGNIZE BETA(2)-GLYCOPROTEIN-I;    MONOCLONAL-ANTIBODIES;    LIPID-BINDING;    NAIVE MICE;    BETA-2-GLYCOPROTEIN-I;    COFACTOR;    INDUCTION;    IDENTIFICATION;    AUTOANTIBODIES;   

DOI  :  10.1161/01.CIR.97.9.900

来源: SCIE

【 摘 要 】

Background-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 beta(2)-glycoprotein I (beta 2GPI) rather than negatively charged phospholipids. However, it has not been determined whether different epitope-specific anti-beta 2GPI antibodies obtained from one patient possess pathogenic properties, Methods and Results-Three beta 2GPI-binding IgM monoclonal antibodies (mAbs) (ILA-1, ILA-3, and ILA-3) were cloned from a patient with APS. The three antibodies were shown to bind beta 2GPI immobilized on irradiated plates, yet only ILA-1 bound beta 2GPI coated onto nonirradiated plates. Furthermore, when using the anti-beta 2GPI enzyme-linked immunosorbent assay, ILA-1 was the only mAb inhibited by fluid phase beta 2GPI. 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 ISM did not produce similar effects, Conclusions-The results of the study demonstrate the differential effects of various populations of anti-beta 2GPI antibodies on endothelial cell activation and on experimental APS.

【 授权许可】

Free