title: Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome.
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 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The results of the study demonstrate the differential effects of various populations of anti-beta2GPI antibodies on endothelial cell activation and on experimental APS.
authors.affiliation: Department of Medicine B Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: Y
authors.initials: Y
authors.lastname: Levy
authors.forename: P
authors.initials: P
authors.lastname: Meroni
authors.forename: M
authors.initials: M
authors.lastname: Damianovich
authors.forename: A
authors.initials: A
authors.lastname: Tincani
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000328:Adult; D000818:Animals; D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002999:Clone Cells; D004727:Endothelium / Q000166:cytology / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology; D053482:beta 2-Glycoprotein I
chemical_list: D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D002308:Cardiolipins; D000939:Epitopes; D006023:Glycoproteins; D007075:Immunoglobulin M; D019010:Vascular Cell Adhesion Molecule-1; D053482:beta 2-Glycoprotein I