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

Abstract

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.

Simvastatin Efficiently Lowers Small LDL-IgG Immune Complex Levels: A Therapeutic Quality beyond the Lipid-Lowering Effect

“…Asciutto et al reported recently that low levels of IgG autoantibodies against the native or MDA-modified apoB peptide p210 are associated with an increased risk of cardiovascular death in patients undergoing carotid endarterectomy [ 71 ]. The activation of macrophages by IgG-IC is determined by the balance between the triggering of activating ITAM-bearing FcγRs and the triggering of inhibitory ITIM-bearing FcγRIIB.…”

Associations between circulating IgG antibodies to Apolipoprotein B100-derived peptide antigens and acute coronary syndrome in a Chinese Han population

“…Fifteen peptide antigens (hAgs) derived from native human ApoB were designed based on the computational prediction of HLA-II restricted epitopes [ 32 ] and on the epitope information for human disease in the Immune Epitope Database ( http://www.iedb.org/ ). These 15 hAgs were all linear antigens with 25–30 amino acid residues that were applied to develop an ELISA in-house for detection of circulating anti-ApoB100 IgG levels based on the method described in our previous studies [ 44 , 45 ]. The sequences of these 15 antigens are given in Table 2 .…”

Modified low-density lipoproteins as biomarkers in diabetes and metabolic syndrome

“…In contrast, some studies show a positive relationship of IgG autoantibodies titers with the development of atherosclerosis (124,147,148). Other authors, however, disagree with this direct relation; thus, Asciutto and coworkers reported that low levels of IgG anti-MDA-LDL correlates with high risk of postoperative death after carotid endarterectomy (149), whereas high levels of these antibodies are associated with decreased plaque inflammation (150). Moreover, studies performed in diabetic mice shows that treatments with anti-oxLDL IgG (151) or AGE-LDL immunization (152) protect against atherosclerosis, thereby suggesting a protective role for IgG autoantibodies.…”