Autoantibody against the amino acid sequence 661–680 in apo B-100 is associated with decreased carotid stenosis and cardiovascular events

Fredrikson, Gunilla Nordin; Schiopu, Alexandru; Berglund, Göran; Alm, Ragnar; Shah, Prediman K.; Nilsson, Jan

doi:10.1016/j.atherosclerosis.2006.12.014

Cited by 53 publications

(42 citation statements)

References 26 publications

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“…In a prospective clinical study we demonstrate that humans who later suffered from acute cardiovascular events had lower levels of antibodies against MDA-laminin than those in the control group. These findings are in line with previous studies, demonstrating an association between high levels of autoantibodies directed against Apo B peptides or aldehyde-modified fibronectin and a lower risk to develop acute cardiovascular events 7,13,14 . Although clinical association studies need to be interpreted with due caution when it comes to mechanisms these results appears to support a protective role of autoantibodies against modified selfantigens such as MDA-laminin.…”

Section: Discussionsupporting

confidence: 93%

Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe−/− mice

Dunér

Berg

et al. 2010

Atherosclerosis

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Section: Discussionsupporting

confidence: 93%

Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe−/− mice

Dunér

Berg

et al. 2010

Atherosclerosis

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“…We have previously shown that high levels of IgG against native as well as aldehyde modified p45 and p210 are associated with less severe coronary and carotid disease as well as with a lower risk for CV events. [31][32][33] In a recent large observational cohort study of high-risk individuals in five European countries McLeod and coworkers 20 demonstrated increased carotid intima-media thickness and a more rapid progression of carotid disease in those with low levels of autoantibodies against native and MDA-modified p210. There is also evidence for an association between low levels of anti-PC IgM and CV events.…”

Section: Discussionmentioning

confidence: 99%

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

Asciutto¹,

Dias²,

Edsfeldt³

et al. 2015

Atherosclerosis

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Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy.Asciutto, Giuseppe; Dias, Nuno; Edsfeldt, Andreas; Alm, Ragnar; Nordin Fredrikson, Gunilla; Goncalves, Isabel; Nilsson, Jan Link to publication Citation for published version (APA): Asciutto, G., Dias, N., Edsfeldt, A., Alm, R., Nordin Fredrikson, G., Goncalves, I., & Nilsson, J. (2015). Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy. Atherosclerosis, 239(2), 289-294. DOI: 10.1016289-294. DOI: 10. /j.atherosclerosis.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Methods: Native (nat) and malondialdehyde (MDA)-modified apoB p210 autoantibodies (IgM-p210nat, IgG-p210nat, IgM-p210MDA and IgG-p210MDA) were analyzed by ELISA from plasma samples of 351 patients at the time they underwent CEA. The incidence of postoperative CV events was assessed using national registers.Results: A total of 52 non-fatal and 15 fatal CV events were registered during the follow-up period (35.1 ± 16.7 months). Patients who suffered from a fatal CV event had significantly lower plasma levels of IgG-p210nat and IgG-p210MDA. Kaplan-Meier curves of event-free survival showed increased CV mortality in patients with levels of IgG-p210nat and IgGp210MDA below the median (Log Rank 7.813, p .005 and 9.105, p .003 respectively). The association between low levels of p210 IgG and fatal post-operative CV events remained significant when adjusting for age, sex, total cholesterol, HDL cholesterol, smoking habits and hypertension in a Cox Proportional Hazard model (hazard ratios (HR) IgG-p210nat below median: HR 6.7 (95% C.I. 1.5-30.6, p .013) and IgG-p210MDA below median: HR 7.8 (95% C.I. 1.7-35.5, p .008).Conclusions: The present findings support the notion that autoantibodies against LDL antigens are involved in the atherosclerotic disease process and suggest that CEA patients with low levels of IgG-p210nat and IgG-p210MDA have an increased risk of post-operative CV death.

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“…These studies have primarily used the p45 (amino acids 661-680) and p210 (amino acids 3136-3155) apo B100 peptides used in the development of immunemodulatory therapies discussed above. Inverse associations have been found between the level of autoantibodies against these apo B100 peptides and the severity of atherosclerosis and subjects that later suffered from acute myocardial infarction has been reported to have lower apo B peptide autoantibodies levels than controls matched for age and gender [44][45][46][47].…”

Section: Biomarkers Of Apo B100 and Oxidized Ldl Autoimmunitymentioning

confidence: 99%

Apolipoprotein B100 autoimmunity and atherosclerosis – disease mechanisms and therapeutic potential

Nilsson

Björkbacka

Fredrikson

2012

Current Opinion in Lipidology

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Purpose of reviewAdaptive immune responses have been shown to play an important role in the atherosclerotic disease process and both pathogenic and protective immunity has been identified. Apolipoprotein (apo) B100 appears to be a key antigen and novel therapies modulating immune responses against apo B100 have shown promising results in experimental models. This review will discuss recent developments in the mechanistic understanding of apo B100 autoimmunity and approaches taken to use this knowledge for development of novel therapies. Recent findingsIt has recently been shown that not only apo B100 modified by oxidation but also nonmodified apo B100 is targeted by autoimmune responses. This implies that a corresponding set of regulatory T cells with the same antigen specificity must exist and that these cells under normal circumstances are able to prevent autoimmunity against LDL. Recent studies also suggest that the athero-protective effect of apo B100 peptide immunization acts by reenforcing the activity of such cells. SummaryThese novel findings suggest that aggravation of plaque inflammation may occur as result of a local loss of tolerance against LDL in the plaque due to insufficient activity of regulatory T cells. Restoration of lost tolerance represents an interesting novel approach for treatment of cardiovascular disease.

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Autoantibody against the amino acid sequence 661–680 in apo B-100 is associated with decreased carotid stenosis and cardiovascular events

Abstract: Autoantibody against the amino acid sequence 661-680 in apo B-100 is associated with decreased carotid stenosis and cardiovascular events.Nordin Fredrikson, Gunilla; Schiopu, Alexandru; Berglund, Göran; Alm, Ragnar; Shah, Prediman K; Nilsson, Jan

Cited by 53 publications

References 26 publications

Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe−/− mice

Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe−/− mice

Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

Apolipoprotein B100 autoimmunity and atherosclerosis – disease mechanisms and therapeutic potential

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