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

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 ε(carboxymethyl)lysine-modified LDL (CML-LDL) as well as antibodies reacting with MDA-LDL, copper-oxidized LDL (OxLDL), CML-...

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Main Authors: Gabriel Virella, Suzanne R. Thorpe, Nathan L. Alderson, M. Brooks Derrick, Charlyne Chassereau, J. Matthew Rhett, Maria F. Lopes-Virella
Format: Article
Language:English
Published: Elsevier 2004-10-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520312591
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author Gabriel Virella
Suzanne R. Thorpe
Nathan L. Alderson
M. Brooks Derrick
Charlyne Chassereau
J. Matthew Rhett
Maria F. Lopes-Virella
author_facet Gabriel Virella
Suzanne R. Thorpe
Nathan L. Alderson
M. Brooks Derrick
Charlyne Chassereau
J. Matthew Rhett
Maria F. Lopes-Virella
author_sort Gabriel Virella
collection DOAJ
description 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 ε(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.
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spelling doaj.art-849fa92d82034bf7958d07475752ed3f2022-12-21T23:18:54ZengElsevierJournal of Lipid Research0022-22752004-10-01451018591867Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodiesGabriel Virella0Suzanne R. Thorpe1Nathan L. Alderson2M. Brooks Derrick3Charlyne Chassereau4J. Matthew Rhett5Maria F. Lopes-Virella6Department 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, SCDepartment 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, SCDepartment 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, SCDepartment 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, SCDepartment 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, SCDepartment 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, SCDepartment 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, SCHumans and laboratory animals recognize human modified LDL as immunogenic. Immune complexes (ICs) isolated from human sera contain malondialdehyde-modified LDL (MDA-LDL) and N ε(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.http://www.sciencedirect.com/science/article/pii/S0022227520312591low density lipoprotein modificationslow density lipoprotein autoantibodiesmodified low density lipoprotein antibodiesimmunology of atherosclerosisautoimmunityatherosclerosis
spellingShingle Gabriel Virella
Suzanne R. Thorpe
Nathan L. Alderson
M. Brooks Derrick
Charlyne Chassereau
J. Matthew Rhett
Maria F. Lopes-Virella
Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies
Journal of Lipid Research
low density lipoprotein modifications
low density lipoprotein autoantibodies
modified low density lipoprotein antibodies
immunology of atherosclerosis
autoimmunity
atherosclerosis
title Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies
title_full Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies
title_fullStr Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies
title_full_unstemmed Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies
title_short Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies
title_sort definition of the immunogenic forms of modified human ldl recognized by human autoantibodies and by rabbit hyperimmune antibodies
topic low density lipoprotein modifications
low density lipoprotein autoantibodies
modified low density lipoprotein antibodies
immunology of atherosclerosis
autoimmunity
atherosclerosis
url http://www.sciencedirect.com/science/article/pii/S0022227520312591
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