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.

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.

• Authors: Y Levy, Y Sherer, A Mathieu, A Cauli, G Passiu, G Sanna, Z Janackovic, M Blank, Y Shoenfeld
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2000 Jul-Aug Vol. 18 Issue 4 Pg. 479-84 ISSN: 0392-856X [Print] Italy
• PMID: 10949723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anticardiolipin
• Antibodies, Monoclonal
• Epitopes
• Glycoproteins
• Immunoglobulin G
• Immunoglobulin M
• beta 2-Glycoprotein I

Topics

• Aged
• Aged, 80 and over
• Animals
• Antibodies, Anticardiolipin (immunology)
• Antibodies, Monoclonal (immunology)
• Antibody Specificity
• Antiphospholipid Syndrome (immunology)
• Epitopes (immunology)
• Glycoproteins (immunology)
• Humans
• Immunization
• Immunoglobulin G (immunology)
• Immunoglobulin M (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Thromboembolism (immunology)
• beta 2-Glycoprotein I