Anti-cardiolipin antibody from a patient with antiphospholipid syndrome (APS) recognizes only an epitope expressed by cardiolipin/β₂-glycoprotein-I (β₂GPI) complex and induces APS

Objective: As the antiphospholipid syndrome (APS) is characterized by antibodies which bind negatively charged phospholipids either directly or mainly through different target epitopes located on the beta-2-glycoprotein-I (β₂GPI) molecule, the aim of this study is to describe an additional target epitope for anti-cardiolipin binding. Methods: The binding characteristics of affinity purified anti-cardiolipin antibodies from a patient with monoclonal gammopathy associated with clinically overt APS were studied; inhibition studies were also carried out. These antibodies were used for the active induction of experimental APS. Results: The affinity purified anti-cardiolipin antibodies were found to bind a target epitope created by the complex of cardiolipin/β₂GPI, while not reacting with a complex composed by another phospholipid (phosphatidylserine/β₂GPI), as confirmed by direct binding and competition assays. Immunization of naive mice with this unique affinity purified anti-cardiolipin antibody resulted in the induction of experimental APS (thrombocytopenia, prolonged coagulation timed and fetal resorptions). The anti-cardiolipin/β₂GPI injected mice developed high titers of mouse anti-cardiolipin/β₂GPI antibodies with the same binding characteristics as the human antibody which was used for disease induction. Conclusion: APS is a unique syndrome that is characterized by a diversity of pathogenic anti-phospholipid antibodies which may explain the diversity of clinical manifestations reported in patients. (C) Copyright Clinical and Experimental Rheumatology 2000.