INDUCTION OF EXPERIMENTAL ANTIPHOSPHOLIPID ANTIBODY SYNDROME IN PL J MICE FOLLOWING IMMUNIZATION WITH BETA(2)GPI/

PROBLEM: Immunization with beta(2)-glycoprotein I (beta(2)GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recentl y we reported early onset of autoimmunity in MRL/++ mice following imm unization with beta(2)GPI. There is a close association between aPL wi th thrombosis, recurrent fetal loss, and intrauterine growth retardati on. 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-old female PL/J mice (12 per group) were studied. Group A was immunized with beta(2)GPI and group B with ovalbumin; gro up C was not immunized. After two booster injections, the mice were te sted for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluores cence. Platelet count and pregnancy outcomes were studied at the age o f 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, 0.091 +/- 0.040 and 0.230 +/- 0.47 for gr oup B, and 0.0435 +/- 0.003 and 0.119 +/- 0.026 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 litter size was significantly s maller 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 g roups A, B, and C, respectively. Seven pregnant mice in group A had co mplete resorption, seven pregnant mice in group B showed focal (partia l) resorption areas, and only one mouse in group C had complete resorp tion of the embryos, as shown by histopathological studies, although t he fecundity rate was similar in the three groups. CONCLUSION: Our dat a suggest a pathogenic role for beta(2)GPI-induced aPL in the developm ent of experimental models of APS in PL/J mice.