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High levels of IgM against methylglyoxal-modified apolipoprotein B100 is associated with less coronary artery calcification in patients with type 2 diabetes.

Engelbertsen, Daniel LU ; Anand, Dhakshinamurthy Vijay; Nordin Fredrikson, Gunilla LU ; Hopkins, David; Corder, Roger; Shah, Prediman K; Lahiri, Avijit; Nilsson, Jan LU and Bengtsson, Eva LU (2012) In Journal of Internal Medicine 271(1). p.82-89
Abstract
Objective: Advanced glycation end products (AGE) have been implicated in diabetic vascular complications through activation of pro-inflammatory genes. AGE-modified proteins are also targeted by the immune system resulting in the generation of AGE-specific autoantibodies, but the association of these immune responses with diabetic vasculopathy remains to be fully elucidated. The aim of this study was to determine whether antibodies against apolipoprotein B100 modified by methylglyoxal (MGO-apoB100) are associated with coronary atherosclerosis in patients with type 2 diabetes. Methods.  We measured antibodies against MGO-apoB100 in plasma from 497 type 2 diabetic patients without clinical signs of cardiovascular disease. Severity of coronary... (More)
Objective: Advanced glycation end products (AGE) have been implicated in diabetic vascular complications through activation of pro-inflammatory genes. AGE-modified proteins are also targeted by the immune system resulting in the generation of AGE-specific autoantibodies, but the association of these immune responses with diabetic vasculopathy remains to be fully elucidated. The aim of this study was to determine whether antibodies against apolipoprotein B100 modified by methylglyoxal (MGO-apoB100) are associated with coronary atherosclerosis in patients with type 2 diabetes. Methods.  We measured antibodies against MGO-apoB100 in plasma from 497 type 2 diabetic patients without clinical signs of cardiovascular disease. Severity of coronary disease was assessed as coronary artery calcium (CAC) imaging. Immunoglobulin (Ig)M and IgG levels recognizing MGO-apoB100 were determined by enzyme-linked immunosorbent assay. Results.  Anti-MGO-apoB100 IgM antibody levels were higher in subjects with a low to moderate CAC score (≤400 Agatston units) than in subjects with a high score (>400 Agatston units; 136.8 ± 4.4 vs. 101.6 ± 7.4 arbitrary units (AU), P < 0.0001) and in subjects demonstrating no progression of CAC during 30 months of follow-up (136.4 ± 5.7 vs. 113.9 ± 6.2 AU in subjects with progression, P < 0.0001). Subjects with a family history of premature myocardial infarction had lower levels of anti-MGO-apoB100 IgM. Female subjects had higher levels of anti-MGO-apoB100 antibodies and lower CAC than men. Accordingly, high levels of IgM against MGO-apoB100 are associated with less severe and a lower risk of progression of coronary disease in subjects with type 2 diabetes. Conclusions.  Although conclusions regarding causal relationships based on epidemiological observations need to be made with caution, our findings suggest the possibility that anti-MGO-apoB100 IgM may be protective in diabetic vasculopathy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
autoantibodies, atherosclerosis, diabetes
in
Journal of Internal Medicine
volume
271
issue
1
pages
82 - 89
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • wos:000298582800009
  • pmid:21668821
  • scopus:83855164160
ISSN
1365-2796
DOI
10.1111/j.1365-2796.2011.02411.x
language
English
LU publication?
yes
id
3767e987-cfb9-41b4-be96-eb4ec7d78dcc (old id 2008122)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21668821?dopt=Abstract
date added to LUP
2011-07-04 14:16:14
date last changed
2017-05-28 04:07:35
@article{3767e987-cfb9-41b4-be96-eb4ec7d78dcc,
  abstract     = {Objective: Advanced glycation end products (AGE) have been implicated in diabetic vascular complications through activation of pro-inflammatory genes. AGE-modified proteins are also targeted by the immune system resulting in the generation of AGE-specific autoantibodies, but the association of these immune responses with diabetic vasculopathy remains to be fully elucidated. The aim of this study was to determine whether antibodies against apolipoprotein B100 modified by methylglyoxal (MGO-apoB100) are associated with coronary atherosclerosis in patients with type 2 diabetes. Methods.  We measured antibodies against MGO-apoB100 in plasma from 497 type 2 diabetic patients without clinical signs of cardiovascular disease. Severity of coronary disease was assessed as coronary artery calcium (CAC) imaging. Immunoglobulin (Ig)M and IgG levels recognizing MGO-apoB100 were determined by enzyme-linked immunosorbent assay. Results.  Anti-MGO-apoB100 IgM antibody levels were higher in subjects with a low to moderate CAC score (≤400 Agatston units) than in subjects with a high score (&gt;400 Agatston units; 136.8 ± 4.4 vs. 101.6 ± 7.4 arbitrary units (AU), P &lt; 0.0001) and in subjects demonstrating no progression of CAC during 30 months of follow-up (136.4 ± 5.7 vs. 113.9 ± 6.2 AU in subjects with progression, P &lt; 0.0001). Subjects with a family history of premature myocardial infarction had lower levels of anti-MGO-apoB100 IgM. Female subjects had higher levels of anti-MGO-apoB100 antibodies and lower CAC than men. Accordingly, high levels of IgM against MGO-apoB100 are associated with less severe and a lower risk of progression of coronary disease in subjects with type 2 diabetes. Conclusions.  Although conclusions regarding causal relationships based on epidemiological observations need to be made with caution, our findings suggest the possibility that anti-MGO-apoB100 IgM may be protective in diabetic vasculopathy.},
  author       = {Engelbertsen, Daniel and Anand, Dhakshinamurthy Vijay and Nordin Fredrikson, Gunilla and Hopkins, David and Corder, Roger and Shah, Prediman K and Lahiri, Avijit and Nilsson, Jan and Bengtsson, Eva},
  issn         = {1365-2796},
  keyword      = {autoantibodies,atherosclerosis,diabetes},
  language     = {eng},
  number       = {1},
  pages        = {82--89},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine},
  title        = {High levels of IgM against methylglyoxal-modified apolipoprotein B100 is associated with less coronary artery calcification in patients with type 2 diabetes.},
  url          = {http://dx.doi.org/10.1111/j.1365-2796.2011.02411.x},
  volume       = {271},
  year         = {2012},
}