title: The Human Autoantibody Response to Apolipoprotein A-I Is Focused on the C-Terminal Helix: A New Rationale for Diagnosis and Treatment of Cardiovascular Disease?
abstract: BACKGROUND
  Cardiovascular disease (CVD) is the leading cause of death worldwide and new approaches for both diagnosis and treatment are required. Autoantibodies directed against apolipoprotein A-I (ApoA-I) represent promising biomarkers for use in risk stratification of CVD and may also play a direct role in pathogenesis.
  
  
  METHODS
  To characterize the anti-ApoA-I autoantibody response, we measured the immunoreactivity to engineered peptides corresponding to the different alpha-helical regions of ApoA-I, using plasma from acute chest pain cohort patients known to be positive for anti-ApoA-I autoantibodies.
  
  
  RESULTS
  Our results indicate that the anti-ApoA-I autoantibody response is strongly biased towards the C-terminal alpha-helix of the protein, with an optimized mimetic peptide corresponding to this part of the protein recapitulating the diagnostic accuracy for an acute ischemic coronary etiology (non-ST segment elevation myocardial infarction and unstable angina) obtainable using intact endogenous ApoA-I in immunoassay. Furthermore, the optimized mimetic peptide strongly inhibits the pathology-associated capacity of anti-ApoA-I antibodies to elicit proinflammatory cytokine release from cultured human macrophages.
  
  
  CONCLUSIONS
  In addition to providing a rationale for the development of new approaches for the diagnosis and therapy of CVD, our observations may contribute to the elucidation of how anti-ApoA-I autoantibodies are elicited in individuals without autoimmune disease.
authors.affiliation: Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pagano
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Gaertner
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cerini
authors.affiliation: Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Mannic
authors.affiliation: Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Satta
authors.affiliation: Pharmaceutical Sciences, Pharma Research and Early Development, F.Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Priscila Camillo
authors.initials: PC
authors.lastname: Teixeira
authors.affiliation: Pharmaceutical Sciences, Pharma Research and Early Development, F.Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Cutler
authors.affiliation: Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.affiliation: Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hartley
mesh_terms: D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000628:therapy*; D002942:Circular Dichroism; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001323:Autoantibodies; D055767:Immobilized Proteins; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D015850:Interleukin-6; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha