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Intrauterine fetal death in mice caused by cytomegalovirus-derived peptide induced aPL antibodies

Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA

M Vega-Ostertag

Antiphospholipid Standardization Laboratory, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

R G Espinola

Antiphospholipid Standardization Laboratory, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

X Liu

Antiphospholipid Standardization Laboratory, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

L Cole

Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA

N T Cox

Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA

P Romagnoli

Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA

K Labat

Antiphospholipid Standardization Laboratory, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

S S Pierangeli

Antiphospholipid Standardization Laboratory, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA, pierans{at}msm.edu

Immunization of mice with ß₂ glycoprotein I (ß₂ GPI) and also with GDKV, a synthetic peptide representing the phospholipid (PL)-binding site of ß₂ GPI, induced pathogenic aPL antibodies that bind and activate endothelial cells, enhanced thrombus formation and caused fetal death in pregnant mice. TIFI is a PL-binding peptide spanning the Thr101-Thr120 of ulb0-hcmva from human cytomegalovirus (CMV), which shares structural similarity with the PL-binding site of ß₂ GPI. Immunization with this peptide induced pathogenic aPL and anti-ß₂ GPI antibodies in mice. These antibodies activated endothelial cells and enhanced thrombus formation in vivo, but whether these antibodies cause fetal death in mice is not known. The objectiveof this study was to examine the effects of these antibodieson pregnancyoutcomein mice. Two groups of pregnantBALB/c mice were injected with either hybridoma supernatant containing D3/AC10, a CMV-peptide-induced monoclonal aPL, at days four, eight and 12 of the pregnancy, 100 m g per mouse (study group) or with culture media alone (control group). The litter size was significantly smaller in the study group (4.80 + 1.15 versus 7.28 + 0.18, t =- 2.526, P < 0.03). In conclusion, aPL induced by CMV peptides may have pathogenic properties similar to human autoimmune aPL. These findings further support the hypothesis that at least in some patients with APS, pathogenic aPL antibodies may be generated by immunization with CMV products during incidental exposure to the virus via a molecular mimicry mechanism.

Key Words: anticardiolipin antibodies • antiphospholipid antibodies • antiphospholipid syndrome • CMV • molecular mimicry • pregnancy loss

Lupus, Vol. 13, No. 1, 17-23 (2004)
DOI: 10.1191/0961203304lu484oa


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