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.
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.
Levy
Y
Y
Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
Sherer
Y
Y
Mathieu
A
A
Cauli
A
A
Passiu
G
G
Sanna
G
G
Janackovic
Z
Z
Blank
M
M
Shoenfeld
Y
Y
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
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D000939:Epitopes; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053482:beta 2-Glycoprotein I