title: Anti-cardiolipin antibody from a patient with antiphospholipid syndrome (APS) recognizes only an epitope expressed by cardiolipin/beta 2-glycoprotein-I (beta 2GPI) complex and induces APS.
abstract: 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 (beta 2GPI) 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/beta 2GPI, while not reacting with a complex composed by another phospholipid (phosphatidylserine/beta 2GPI), 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/beta 2GPI injected mice developed high titers of mouse anti-cardiolipin/beta 2GPI antibodies with the same binding characteristics as the human antibody which was used for disease induction.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Levy
authors.forename: Y
authors.initials: Y
authors.lastname: Sherer
authors.forename: A
authors.initials: A
authors.lastname: Mathieu
authors.forename: A
authors.initials: A
authors.lastname: Cauli
authors.forename: G
authors.initials: G
authors.lastname: Passiu
authors.forename: G
authors.initials: G
authors.lastname: Sanna
authors.forename: Z
authors.initials: Z
authors.lastname: Janackovic
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013923:Thromboembolism / Q000276:immunology; D053482:beta 2-Glycoprotein I
chemical_list: D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D000939:Epitopes; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053482:beta 2-Glycoprotein I