title: Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo.
abstract: OBJECTIVE
  To characterize the binding and functional properties of antiphospholipid antibodies (aPL) induced by immunization with a viral peptide and to determine whether aPL are pathogenic in vivo.
  
  
  METHODS
  Ten murine monoclonal aPL were generated from spleen cells of PL/J mice immunized with TIFI, a phospholipid-binding peptide spanning Thr(101)-Thr(120) of ULB0-HCMVA from human cytomegalovirus (CMV), which shares structural similarity with the phospholipid-binding site of beta(2)-glycoprotein I (beta(2)GPI).
  
  
  RESULTS
  The antibodies generated had aPL activity that was inhibited by cardiolipin liposomes, and this inhibition was enhanced in the presence of beta(2)GPI. Some of the antibodies exhibited binding to cultured endothelial cells in vitro, and some had lupus anticoagulant activity. Injection with 2 of the monoclonal aPL in mice resulted in a significant increase in the number of leukocytes adhering to endothelial cells and enhanced thrombus formation in vivo.
  
  
  CONCLUSIONS
  These results indicate that aPL induced by immunization with a phospholipid-binding CMV peptide are pathogenic in vivo. The results also suggest a mechanism (molecular mimicry) by which pathogenic aPL may be generated in patients with antiphospholipid syndrome.
authors.affiliation: Department of Medicine, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495, USA. Aghara@pol.net
authors.forename: Azzudin E
authors.initials: AE
authors.lastname: Gharavi
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Pierangeli
authors.forename: Ricardo G
authors.initials: RG
authors.lastname: Espinola
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Liu
authors.forename: Margaret
authors.initials: M
authors.lastname: Colden-Stanfield
authors.forename: E Nigel
authors.initials: EN
authors.lastname: Harris
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D007114:Immunization; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D013927:Thrombosis / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology; D053482:beta 2-Glycoprotein I
chemical_list: D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D014764:Viral Proteins; D053482:beta 2-Glycoprotein I