Early onset of autoimmunity in MRL/++ mice following immunization with β₂ glycoprotein I

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with β₂ glycoprotein I (β₂GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by β₂GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with β₂GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all β₂GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting crossreactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in β₂GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that β₂GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.