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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7840525
- author
- 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
- organization
- publishing date
- 2015
- 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
- pmid:26290603
- 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
- 2016-04-01 10:14:28
- date last changed
- 2022-02-24 23:45:50
@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}},
doi = {{10.4049/jimmunol.1402869}},
volume = {{195}},
year = {{2015}},
}