Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo.
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.
Gharavi
Azzudin E
AE
Department of Medicine, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495, USA. Aghara@pol.net
Pierangeli
Silvia S
SS
Espinola
Ricardo G
RG
Liu
Xiaowei
X
Colden-Stanfield
Margaret
M
Harris
E Nigel
EN
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
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D014764:Viral Proteins; D053482:beta 2-Glycoprotein I