Anti-cardiolipin antibody from a patient with antiphospholipid syndrome (APS) recognizes only an epitope expressed by cardiolipin/beta(2)-glycoprotein-I (beta(2)GPI) complex and induces APS

Objective As the antiphospholipid syndrome (APS) is characterized by antibodies which bind negatively charged phospholipids either directly or mainly through di fferent target epitopes located on the beta-2-glycoprotein-1 (beta(2)GPI) m olecule, 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 antibodie s from a patient with monoclonal gammopathy associated with clinically over t APS were studied; inhibition studies were also carried out. These antibod ies were used for the active induction of experimental APS. Results The affinity purified anti-cardiolipin antibodies were found to bind a targ et epitope created by the complex of cardiolipin/beta(2)GPI, while not reac ting with a complex composed by another phospholipid (phosphatidylserine/be ta(2)GPI), as confirmed by direct binding and competition assays. Immunizat ion of naive mice with this unique affinity purified anticardiolipin antibo dy resulted in the induction of experimental APS (thrombocytopenia, prolong ed coagulation timed and fetal resorptions). The anti-cardiolipin/beta(2)GP I injected mice developed high titers of mouse anti-cardiolipin/beta(2)GPI antibodies with the same binding characteristics as the human antibody whic h 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 m anifestations reported in patients.