Problem: Immunization with beta 2-glycoprotein I (beta 2 GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/(+2) mice following immunization with beta 2 GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of beta 2 GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J).
Method: Three groups of seven-week female PL/J mice (12 per group) were studied. Group A was immunized with beta 2 GPI and group B with ovalbumin; group C was not not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks.
Results: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72 +/- 0.6 and 0.699 +/- 0.25 for group A, 0.09 +/- 0.040 and 0.230 +/- 0.47 for group B, and 0.0435 +/- 0.003 and 0.119 +/- 0.26 for group C (comparing group A with groups B and C combined, P < 0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P < 0.001). The platelet counts were not significantly different among the three groups. The titer size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, by only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups.
Conclusion: Our data suggest a pathogenic role for beta 2 GPI-induced aPL in the development of experimental models of APS in PL/J mice.