Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome

• Published in: Circulation (New York, N.Y.) N.Y.), 1998-03, Vol.97 (9), p.900-906
• Main Authors: George, J, Blank, M, Levy, Y, Meroni, P, Damianovich, M, Tincani, A, Shoenfeld, Y
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antibodies, Anticardiolipin; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Antiphospholipid Syndrome - immunology; beta 2-Glycoprotein I; Cardiolipins - immunology; Cardiolipins - metabolism; Cells, Cultured; Clone Cells; Endothelium - cytology; Endothelium - immunology; Epitopes; Female; Glycoproteins - immunology; Glycoproteins - metabolism; Humans; Immunoglobulin M; Mice; Mice, Inbred BALB C; Pregnancy; Umbilical Veins - cytology; Vascular Cell Adhesion Molecule-1 - immunology
• ISSN: 0009-7322; 1524-4539

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.