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.

APPROACH AND 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: Olga McLeod, Angela Silveira, Gunilla N Fredrikson, Karl Gertow, Damiano Baldassarre, Fabrizio Veglia, Bengt Sennblad, Rona J Strawbridge, Malin Larsson, Karin Leander, Bruna Gigante, Jussi Kauhanen, Rainer Rauramaa, Andries J Smit, Elmo Mannarino, Philippe Giral, Steve E Humphries, Elena Tremoli, Ulf de Faire, John Ohrvik, Jan Nilsson, Anders Hamsten
• Journal: Atherosclerosis (Atherosclerosis) Vol. 232 Issue 1 Pg. 242-8 (Jan 2014) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 24401246 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Apolipoprotein B-100
• Autoantibodies
• Epitopes
• Immunoglobulin G
• Peptides
• Malondialdehyde

Topics

• Aged
• Apolipoprotein B-100 (chemistry, immunology)
• Atherosclerosis (immunology, prevention & control)
• Autoantibodies (blood)
• Carotid Intima-Media Thickness
• Cohort Studies
• Disease Progression
• Epitopes (blood, chemistry)
• Europe
• Female
• Genotype
• Humans
• Immunoglobulin G (blood)
• Inflammation
• Longitudinal Studies
• Male
• Malondialdehyde (chemistry)
• Middle Aged
• Peptides (chemistry, immunology)
• Risk Factors
• Time Factors