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(Circulation. 2001;103:941.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both ß₂-Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Sohvi Hörkkö, MD, PhD; Tsaiwei Olee, PhD; Lian Mo, PhD; D. Ware Branch, MD; Virgil L. Woods, Jr, MD; Wulf Palinski, MD; Pojen P. Chen, PhD; Joseph L. Witztum, MD

From the Department of Medicine, University of California, San Diego, and the Department of Obstetrics and Gynecology, University of Utah, Health Sciences Center, Salt Lake City (D.W.B.).

Correspondence to Joseph L. Witztum, MD, or Sohvi Hörkkö, MD, PhD, Dept of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0682. E-mail jwitztum@ucsd.edu or shorkko{at}ucsd.edu

Background—We recently suggested that many anticardiolipin antibodies bind only to oxidized cardiolipin (OxCL) and/or to OxCL–ß₂-glycoprotein 1 (ß₂GP1) adducts but not to a "reduced" cardiolipin that is unable to undergo oxidation. To test this hypothesis, we investigated 24 sera, 4 protein A–purified IgG fractions, and 3 human monoclonal antibodies that were all isolated from patients with antiphospholipid antibody syndrome (APS); testing 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 ß₂GP1 (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 ß₂GP1 but only when the ß₂GP1 was plated on microtiter wells coated with OxCL. All 3 monoclonal antibodies bound only to OxCL. On Western blots, IS4 and LJB8 bound to ß₂GP1 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 ß₂GP1 with oxidation products of CL made it 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 needed to generate epitopes for many anticardiolipin antibodies and that some of these epitopes are covalent adducts of OxCL with ß₂GP1 or apoB.

Key Words: antibodies, antiphospholipid • lipoproteins • autoimmunity

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