Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis

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 ÖhrvikJan Nilsson, Anders Hamsten

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)242-248
Number of pages7
JournalAtherosclerosis
Volume232
Issue number1
DOIs
Publication statusPublished - Jan 2014

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Apolipoprotein B-100
Carotid Intima-Media Thickness
Autoantibodies
Atherosclerosis
Peptides
Immunoglobulin M
Immunoglobulin G
Malondialdehyde
Common Carotid Artery
Autoimmunity
Longitudinal Studies
Epitopes
Cohort Studies
Cardiovascular Diseases

Keywords

  • Carotid ultrasound
  • Intima-media thickness
  • Malondialdehyde-modified apoB-100 peptide 210
  • Native apoB-100 peptide 210
  • Progression

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis. / McLeod, Olga; Silveira, Angela; Fredrikson, Gunilla N.; Gertow, Karl; Baldassarre, Damiano; Veglia, Fabrizio; Sennblad, Bengt; Strawbridge, Rona J.; Larsson, Malin; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Humphries, Steve E.; Tremoli, Elena; de Faire, Ulf; Öhrvik, John; Nilsson, Jan; Hamsten, Anders.

In: Atherosclerosis, Vol. 232, No. 1, 01.2014, p. 242-248.

Research output: Contribution to journalArticle

McLeod, O, Silveira, A, Fredrikson, GN, Gertow, K, Baldassarre, D, Veglia, F, Sennblad, B, Strawbridge, RJ, Larsson, M, Leander, K, Gigante, B, Kauhanen, J, Rauramaa, R, Smit, AJ, Mannarino, E, Giral, P, Humphries, SE, Tremoli, E, de Faire, U, Öhrvik, J, Nilsson, J & Hamsten, A 2014, 'Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis', Atherosclerosis, vol. 232, no. 1, pp. 242-248. https://doi.org/10.1016/j.atherosclerosis.2013.11.041
McLeod, Olga ; Silveira, Angela ; Fredrikson, Gunilla N. ; Gertow, Karl ; Baldassarre, Damiano ; Veglia, Fabrizio ; Sennblad, Bengt ; Strawbridge, Rona J. ; Larsson, Malin ; Leander, Karin ; Gigante, Bruna ; Kauhanen, Jussi ; Rauramaa, Rainer ; Smit, Andries J. ; Mannarino, Elmo ; Giral, Philippe ; Humphries, Steve E. ; Tremoli, Elena ; de Faire, Ulf ; Öhrvik, John ; Nilsson, Jan ; Hamsten, Anders. / Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis. In: Atherosclerosis. 2014 ; Vol. 232, No. 1. pp. 242-248.
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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.",
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T1 - Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis

AU - McLeod, Olga

AU - Silveira, Angela

AU - Fredrikson, Gunilla N.

AU - Gertow, Karl

AU - Baldassarre, Damiano

AU - Veglia, Fabrizio

AU - Sennblad, Bengt

AU - Strawbridge, Rona J.

AU - Larsson, Malin

AU - Leander, Karin

AU - Gigante, Bruna

AU - Kauhanen, Jussi

AU - Rauramaa, Rainer

AU - Smit, Andries J.

AU - Mannarino, Elmo

AU - Giral, Philippe

AU - Humphries, Steve E.

AU - Tremoli, Elena

AU - de Faire, Ulf

AU - Öhrvik, John

AU - Nilsson, Jan

AU - Hamsten, Anders

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

KW - Carotid ultrasound

KW - Intima-media thickness

KW - Malondialdehyde-modified apoB-100 peptide 210

KW - Native apoB-100 peptide 210

KW - Progression

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