Differential Effects of Anti–β 2 -Glycoprotein I Antibodies on Endothelial Cells and on the Manifestations of Experimental Antiphospholipid Syndrome

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Abstract
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 β2-glycoprotein I (β2GPI) rather than negatively charged phospholipids. However, it has not been determined whether different epitope-specific anti-β2GPI antibodies obtained from one patient possess pathogenic properties. Methods and Results—Three β2GPI-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 β2GPI immobilized on irradiated plates, yet only ILA-1 bound β2GPI coated onto nonirradiated plates. Furthermore, when using the anti-β2GPI enzyme-linked immunosorbent assay, ILA-1 was the only mAb inhibited by fluid phase β2GPI. ILA-1 and ILA-3, but not ILA-4, induced adherence ...