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

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

Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425

Corresponding Author: virellag{at}musc.edu

Humans and laboratory animals recognize human modified LDL as immunogenic. Immune complexes (IC) isolated from human sera contain malondialdehyde-modified LDL (MDA-LDL) and Ne(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 rec-ognize 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, 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 ApoB-rich lipoproteins isolated from IC, suggesting that laboratory-generated epitopes are expressed by in vivo-modified LDL, although 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, while rabbit antibodies can be used to detect in vivo-modified human LDL.

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