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Low Levels of IgM Antibodies against an Advanced Glycation Endproduct-Modified Apolipoprotein B100 Peptide Predict Cardiovascular Events in Nondiabetic Subjects.

Engelbertsen, Daniel LU ; Vallejo, Jenifer LU ; Quách, Tâm Dan; Nordin Fredrikson, Gunilla LU ; Alm, Ragnar LU ; Hedblad, Bo LU ; Björkbacka, Harry LU ; Rothstein, Thomas L; Nilsson, Jan LU and Bengtsson, Eva LU (2015) In Journal of Immunology 195(7). p.3020-3025
Abstract
Increased glucose levels are associated with the generation of advanced glycation endproduct (AGE) modifications. Interaction between AGE-modified plaque components and immune cells is believed to have an important role in the development of vascular complications in diabetes. Methylglyoxal (MGO) is one type of reactive aldehyde that gives rise to AGE modification. The present study analyzed whether autoantibodies against MGO-modified epitopes of the low-density lipoprotein apolipoprotein B (apoB) 100 predict cardiovascular events. A library consisting of 302 peptides comprising the complete apoB100 molecule was screened to identify peptides targeted by MGO-specific autoantibodies. Peptide (p) 220 (apoB amino acids 3286-3305) was... (More)
Increased glucose levels are associated with the generation of advanced glycation endproduct (AGE) modifications. Interaction between AGE-modified plaque components and immune cells is believed to have an important role in the development of vascular complications in diabetes. Methylglyoxal (MGO) is one type of reactive aldehyde that gives rise to AGE modification. The present study analyzed whether autoantibodies against MGO-modified epitopes of the low-density lipoprotein apolipoprotein B (apoB) 100 predict cardiovascular events. A library consisting of 302 peptides comprising the complete apoB100 molecule was screened to identify peptides targeted by MGO-specific autoantibodies. Peptide (p) 220 (apoB amino acids 3286-3305) was identified as a major target. Baseline IgM and IgG against MGO-peptide 220 (p220) were measured in 700 individuals from the Malmö Diet and Cancer Cohort. A total of 139 cardiovascular events were registered during the 15-y follow-up period. Controlling for major cardiovascular risk factors demonstrated that subjects in the lowest tertile of MGO-p220 IgM had an increased risk for cardiovascular events (hazard ratio [95% confidence interval]: 2.07 [1.22-3.50]; ptrend = 0.004). Interestingly, the association between MGO-p220 IgM and cardiovascular events remained and even tended to become stronger when subjects with prevalent diabetes were excluded from the analysis (2.51 [1.37-4.61]; ptrend = 0.002). MGO-p220 IgM was inversely associated with blood glucose, but not with oxidized low-density lipoprotein. Finally, we demonstrate that anti-MGO-p220 IgM is produced by B1 cells. These data show that subjects with low levels of IgM recognizing MGO-modified p220 in apoB have an increased risk to develop cardiovascular events and that this association is present in nondiabetic subjects. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
195
issue
7
pages
3020 - 3025
publisher
American Association of Immunologists
external identifiers
  • pmid:26290603
  • wos:000361741200009
  • scopus:84942465581
ISSN
1550-6606
DOI
10.4049/jimmunol.1402869
language
English
LU publication?
yes
id
b6bc7b09-92fd-4d88-8196-8b036f79a1dd (old id 7840525)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26290603?dopt=Abstract
date added to LUP
2015-09-06 15:35:59
date last changed
2017-06-11 03:07:25
@article{b6bc7b09-92fd-4d88-8196-8b036f79a1dd,
  abstract     = {Increased glucose levels are associated with the generation of advanced glycation endproduct (AGE) modifications. Interaction between AGE-modified plaque components and immune cells is believed to have an important role in the development of vascular complications in diabetes. Methylglyoxal (MGO) is one type of reactive aldehyde that gives rise to AGE modification. The present study analyzed whether autoantibodies against MGO-modified epitopes of the low-density lipoprotein apolipoprotein B (apoB) 100 predict cardiovascular events. A library consisting of 302 peptides comprising the complete apoB100 molecule was screened to identify peptides targeted by MGO-specific autoantibodies. Peptide (p) 220 (apoB amino acids 3286-3305) was identified as a major target. Baseline IgM and IgG against MGO-peptide 220 (p220) were measured in 700 individuals from the Malmö Diet and Cancer Cohort. A total of 139 cardiovascular events were registered during the 15-y follow-up period. Controlling for major cardiovascular risk factors demonstrated that subjects in the lowest tertile of MGO-p220 IgM had an increased risk for cardiovascular events (hazard ratio [95% confidence interval]: 2.07 [1.22-3.50]; ptrend = 0.004). Interestingly, the association between MGO-p220 IgM and cardiovascular events remained and even tended to become stronger when subjects with prevalent diabetes were excluded from the analysis (2.51 [1.37-4.61]; ptrend = 0.002). MGO-p220 IgM was inversely associated with blood glucose, but not with oxidized low-density lipoprotein. Finally, we demonstrate that anti-MGO-p220 IgM is produced by B1 cells. These data show that subjects with low levels of IgM recognizing MGO-modified p220 in apoB have an increased risk to develop cardiovascular events and that this association is present in nondiabetic subjects.},
  author       = {Engelbertsen, Daniel and Vallejo, Jenifer and Quách, Tâm Dan and Nordin Fredrikson, Gunilla and Alm, Ragnar and Hedblad, Bo and Björkbacka, Harry and Rothstein, Thomas L and Nilsson, Jan and Bengtsson, Eva},
  issn         = {1550-6606},
  language     = {eng},
  number       = {7},
  pages        = {3020--3025},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Low Levels of IgM Antibodies against an Advanced Glycation Endproduct-Modified Apolipoprotein B100 Peptide Predict Cardiovascular Events in Nondiabetic Subjects.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1402869},
  volume       = {195},
  year         = {2015},
}