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

Abstract

Immunization of mice with β2 glycoprotein I (β2 GPI) and also with GDKV, a synthetic peptide representing the phospholipid (PL)-binding site of β2 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 β2 GPI. Immunization with this peptide induced pathogenic aPL and anti-β2 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.