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Journal of Lipid Research, Vol. 45, 1859-1867, October 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies

Gabriel Virella^1,*, Suzanne R. Thorpe, Nathan L. Alderson, M. Brooks Derrick^*,, Charlyne Chassereau^*,, J. Matthew Rhett^*, and Maria F. Lopes-Virella

^* Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC
Department of Medicine, Division of Endocrinology-Metabolism-Nutrition, Medical University of South Carolina, and Ralph H. Johnson Department of Veteran Affairs Medical Center, Charleston, SC

¹ To whom correspondence should be addressed. e-mail: virellag{at}musc.edu

Humans and laboratory animals recognize human modified LDL as immunogenic. Immune complexes (ICs) isolated from human sera contain malondialdehyde-modified LDL (MDA-LDL) and N (carboxymethyl)lysine-modified LDL (CML-LDL) as well as antibodies reacting with MDA-LDL, copper-oxidized LDL (OxLDL), CML-LDL, and advanced glycosylation end product (AGE)-modified LDL. OxLDL and AGE-LDL antibodies isolated from human sera recognize the same LDL modifications and do not react with modified non-LDL proteins. Rabbit antibodies have different reactivity patterns: MDA-LDL antibodies react strongly with MDA-LDL and MDA-BSA but weakly with OxLDL; OxLDL antibodies react strongly with OxLDL and weakly with MDA-LDL; CML-LDL antibodies react with CML-LDL > CML-BSA > AGE-LDL > OxLDL; AGE-LDL antibodies react strongly with AGE-LDL, react weakly with OxLDL, and do not react with CML-LDL. Thus, human and rabbit antibodies seem to recognize different epitopes. Capture assays carried out with all rabbit antibodies showed binding of apolipoprotein B-rich lipoproteins isolated from ICs, suggesting that laboratory-generated epitopes are expressed by in vivo-modified LDL, although they are not necessarily recognized by the human immune system.

Thus, the definition of immunogenic forms of modified LDL eliciting human autoimmune responses requires the isolation and characterization of autoantibodies and modified LDL from human samples, whereas rabbit antibodies can be used to detect in vivo-modified human LDL.

Supplementary key words low density lipoprotein modifications • low density lipoprotein autoantibodies • modified low density lipoprotein antibodies • immunology of atherosclerosis • autoimmunity • atherosclerosis

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