Immunization of naive BALB/c mice with human β₂-glycoprotein I breaks tolerance to the murine molecule

Objective. Immunization of naive mice with β₂ glycoprotein I (β₂GPI) leads to the generation of pathogenic anticardiolipin antibodies associated with clinical manifestations of the antiphospholipid syndrome (APS). The aim of this study was to determine whether immunization of naive mice with human β₂GPI, which shares homology with mouse β₂GPI molecules, breaks tolerance to murine β₂GPI and leads to the generation of anti-mouse β₂GPI. Methods. Twenty-four female BALB/c mice were immunized in the footpads with 10 μg of human β₂GPI. Twelve age- and sex-matched BALB/c mice were immunized in the same manner with Freund's complete adjuvant and served as controls. The reactivity of whole sera, polyclonal IgG, and affinity-purified anti-β₂GPI IgG antibodies against human, bovine, and mouse β₂GPI was evaluated by enzyme-linked immunosorbent assay. Results. High titers of anti-human β₂GPI IgG antibodies were detected I month after immunization. Progressively increasing titers against murine and bovine β₂GPI were recorded 1-4 months after injection. Conclusion. Immunization of mice with human β₂GPI resulted in the generation of antibodies reacting with human, bovine, and murine β₂GPI. The loss of tolerance to mouse β₂GPI is attributable to the high interspecies homology of β₂GPI. These results may point to molecular mimicry as a possible cause of APS.