title: Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases.
abstract: Autoantibodies to apolipoprotein A-I (anti-apoA-I IgG) have been shown to be both markers and mediators of cardiovascular disease, promoting atherogenesis and unstable atherosclerotic plaque. Previous studies have shown that high levels of anti-apoA-I IgGs are independently associated with major adverse cardiovascular events in patients with myocardial infarction. Autoantibody responses to apoA-I can be polyclonal and it is likely that more than one epitope may exist. To identify the specific immunoreactive peptides in apoA-I, we have developed a set of methodologies and procedures to isolate, purify, and identify novel apoA-I endogenous epitopes. First, we generated high purity apoA-I from human plasma, using thiophilic interaction chromatography followed by enzymatic digestion specifically at lysine or arginine residues. Immunoreactivity to the different peptides generated was tested by ELISA using serum obtained from patients with acute myocardial infarction and high titers of autoantibodies to native apoA-I. The immunoreactive peptides were further sequenced by mass spectrometry. Our approach successfully identified two novel immunoreactive peptides, recognized by autoantibodies from patients suffering from myocardial infarction, who contain a high titer of anti-apoA-I IgG. The discovery of these epitopes may open innovative prognostic and therapeutic opportunities potentially suitable to improve current cardiovascular risk stratification.
authors.affiliation: From the Pharma Research and Early Development, Roche Innovation Center, 4070 Basel, the Department of Genetics and Laboratory Medicine, Division of Laboratory Medicine, 1205 Geneva University Hospitals, 1205 Geneva, and priscila.teixeira@roche.com.
authors.forename: Priscila Camillo
authors.initials: PC
authors.lastname: Teixeira
authors.affiliation: From the Pharma Research and Early Development, Roche Innovation Center, 4070 Basel.
authors.forename: Axel
authors.initials: A
authors.lastname: Ducret
authors.affiliation: From the Pharma Research and Early Development, Roche Innovation Center, 4070 Basel.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ferber
authors.affiliation: the Department of Immunopathology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Gaertner
authors.affiliation: the Department of Immunopathology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hartley
authors.affiliation: the Department of Genetics and Laboratory Medicine, Division of Laboratory Medicine, 1205 Geneva University Hospitals, 1205 Geneva, and.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pagano
authors.affiliation: From the Pharma Research and Early Development, Roche Innovation Center, 4070 Basel.
authors.forename: Michelle
authors.initials: M
authors.lastname: Butterfield
authors.affiliation: From the Pharma Research and Early Development, Roche Innovation Center, 4070 Basel.
authors.forename: Hanno
authors.initials: H
authors.lastname: Langen
authors.affiliation: the Department of Genetics and Laboratory Medicine, Division of Laboratory Medicine, 1205 Geneva University Hospitals, 1205 Geneva, and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.affiliation: From the Pharma Research and Early Development, Roche Innovation Center, 4070 Basel.
authors.forename: Paul
authors.initials: P
authors.lastname: Cutler
mesh_terms: D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D015415:Biomarkers / Q000032:analysis; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D020539:Sequence Analysis, Protein
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides
keywords: Anti-apolipoprotein A-I; Autoimmune Disease; Cardiovascular Disease; Epitope Mapping; Immunoreactive Peptides; Mass Spectrometry (MS); Protein Purification