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

Y. Levy, Y. Sherer, A. Mathieu, A. Cauli, G. Passiu, G. Sanna, Z. Janackovic, M. Blank, Y. Shoenfeld

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 (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.

Original languageEnglish
Pages (from-to)479-484
Number of pages6
JournalClinical and Experimental Rheumatology
Volume18
Issue number4
StatePublished - 23 Aug 2000
Externally publishedYes

Keywords

  • Anticardiolipin antibody
  • Antiphospholipid syndrome
  • Beta-2-glycoprotein I
  • Monoclonal gammopathy
  • Thromboembolism

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