title: Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis.
abstract: OBJECTIVE
  Experimental studies have suggested that autoimmunity is involved in atherosclerosis and provided evidence that both protective and pro-atherogenic immune responses exist. This concept has received support from small clinical studies implicating autoantibodies directed against apolipoprotein B-100 (apoB-100) in human atherosclerosis. We examined circulating autoantibodies directed against native and malondialdehyde (MDA)-modified epitope p210 of apoB-100 (IgG-p210nat and IgM-p210MDA) in relation to early atherosclerosis in a large, European longitudinal cohort study of healthy high-risk individuals.
  
  
  RESULTS
  IgG-p210nat and IgM-p210MDA were quantified in baseline plasma samples of 3430 participants in the IMPROVE study and related to composite and segment-specific measures of severity and rate of progression of carotid intima-media thickness (cIMT) determined at baseline and after 30 months. IgM-p210MDA autoantibody levels were independently related to several cIMT measures both in the common carotid artery and in the carotid bulb, including measures of cIMT progression, higher levels being associated with lower cIMT or slower cIMT progression. Consistent inverse relationships were also found between plasma levels of IgG-p210nat and baseline composite measures of cIMT. These associations disappeared when adjusting for established and emerging risk factors, and there were no associations with rate of cIMT progression besides in certain secondary stratified analyses.
  
  
  CONCLUSIONS
  The present study provides further evidence of involvement of autoantibodies against native and MDA-modified apoB-100 peptide 210 in cardiovascular disease in humans and demonstrates that these associations are present already at a subclinical stage of the disease.
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Electronic address: Olga.Piksasova@ki.se.
authors.forename: Olga
authors.initials: O
authors.lastname: McLeod
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.affiliation: Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Gunilla N
authors.initials: GN
authors.lastname: Fredrikson
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Gertow
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Baldassarre
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Sennblad
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rona J
authors.initials: RJ
authors.lastname: Strawbridge
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Leander
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bruna
authors.initials: B
authors.lastname: Gigante
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Kauhanen
authors.affiliation: Foundation for Research in Health, Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rauramaa
authors.affiliation: Department of Medicine, University Medical Center Groningen, The Netherlands.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elmo
authors.initials: E
authors.lastname: Mannarino
authors.affiliation: Assistance Publique - Hopitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Giral
authors.affiliation: Centre for Cardiovascular Genetics, University College London, United Kingdom.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Ohrvik
authors.affiliation: Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
mesh_terms: D000368:Aged; D053299:Apolipoprotein B-100 / Q000737:chemistry / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology* / Q000517:prevention & control*; D001323:Autoantibodies / Q000097:blood*; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D018450:Disease Progression; D000939:Epitopes / Q000097:blood* / Q000737:chemistry; D005060:Europe; D005260:Female; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007249:Inflammation; D008137:Longitudinal Studies; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D012307:Risk Factors; D013997:Time Factors
chemical_list: D053299:Apolipoprotein B-100; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D008315:Malondialdehyde
keywords: Carotid ultrasound; Intima-media thickness; Malondialdehyde-modified apoB-100 peptide 210; Native apoB-100 peptide 210; Progression