Anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)-glycoprotein 1 and oxidized low-density lipoprotein
S. Horkko et al., Anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)-glycoprotein 1 and oxidized low-density lipoprotein, CIRCULATION, 103(7), 2001, pp. 941-946
Citations number
33
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background--We recently suggested that many anticardiolipin antibodies bind
only to oxidized cardiolipin (OxCL) and/or to OxCL-beta (2)-glycoprotein 1
(beta (2)GP1) adducts but not to a "reduced" cardiolipin that is unable to
undergo oxidation, To test this hypothesis, we investigated 24 sera, 4 pro
tein A-purified IgG fractions, and 3 human monoclonal antibodies that were
all isolated from patients with antiphospholipid antibody syndrome (APS); t
esting was also performed in 7 controls. Two monoclonal antibodies (IS3 and
IS4) were selected for binding to CL and one was selected for binding to b
eta (2)GP1 (LJB8).
Methods and Results--By chemiluminescent immunoassay, all APS sera samples
bound only to OxCL and not to reduced CL, and the binding was inhibited >95
% by OxCL but not reduced CL, All purified IgG fractions bound to beta (2)G
P1 but only when the beta (2)GP1 was plated on microtiter wells coated with
OxCL. All 3 monoclonal antibodies bound only to OxCL. On Western blots, IS
4 and LJB8 bound to beta (2)GP1 as well as to delipidated apoB of oxidized
LDL but not to native apoB. IS3 also bound to oxidized apoB on Western blot
. Covalent modification of beta (2)GP1 with oxidation products of CL made i
t more antigenic for APS serum samples, for purified IgG fractions, and for
the monoclonal antibodies.
Conclusions--These data support the hypothesis that oxidation of CL is need
ed to generate epitopes for many anticardiolipin antibodies and that some o
f these epitopes are covalent adducts of OxCL with beta (2)GP1 or apoB.