Antiphospholipid antibody syndrome (APS) is characterized by autoantibodies against negatively charged phospholipids in the serum, and clinically by multiple thromboses, thrombocytopenia, and recurrent fetal loss. The mechanism(s) by which the antibodies cause the clinical picture are not clear. We review the possible mechanisms of action of antiphospholipid (aPL) antibodies. Apparently, aPL antibodies act by interfering with coagulation, involving both endothelial cells, platelets, and humoral components, and affect pregnancy outcome by interfering with embryo implantation and fetal development.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta(2) glycoprotein I (beta(2)GPI) 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 beta(2)GPI 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 beta(2)GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the 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 beta(2)GPI-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 beta(2)GPI-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, beta(2)GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.

Three types of Experimental Animal Models have been used to investigate APA. 1) Passive transfer of APA to nocive mice. Branch et al injected pregnant Balb/c mice with purified IgG APA from patients with recurrent fetal loss. 2) Active immunization with APA. Backimer et al immunized Balb/c mice with a human monoclonal APA carrying the pathogenic idiotypes. 3) Immunization with beta 2 glycoprotein I (beta 2 GPI) (APA cofactor). Using affinity chromatography, we separated two distinct populations of antibodies. One was specific for beta 2GPI without binding to PL. Another population had a dual specificity for PL and beta 2GPI.