Differential effects of anti-β2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome

Jacob George, Miri Blank, Yair Levy, Pierluigi Meroni, Maya Damianovich, Angela Tincani, Yehuda Shoenfeld

Research output: Contribution to journalArticlepeer-review

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 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-β2GPI antibodies on endothelial cell activation and on experimental APS.

Original languageEnglish
Pages (from-to)900-906
Number of pages7
JournalCirculation
Volume97
Issue number9
Publication statusPublished - Mar 10 1998

Keywords

  • Adhesion molecules
  • Antibodies
  • Endothelium
  • Immune system

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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