title: High levels of IgM against methylglyoxal-modified apolipoprotein B100 are associated with less coronary artery calcification in patients with type 2 diabetes.
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 (>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.
authors.affiliation: Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. daniel.engelbertsen@med.lu.se
authors.forename: D
authors.initials: D
authors.lastname: Engelbertsen
authors.forename: D V
authors.initials: DV
authors.lastname: Anand
authors.forename: G N
authors.initials: GN
authors.lastname: Fredrikson
authors.forename: D
authors.initials: D
authors.lastname: Hopkins
authors.forename: R
authors.initials: R
authors.lastname: Corder
authors.forename: P K
authors.initials: PK
authors.lastname: Shah
authors.forename: A
authors.initials: A
authors.lastname: Lahiri
authors.forename: J
authors.initials: J
authors.lastname: Nilsson
authors.forename: E
authors.initials: E
authors.lastname: Bengtsson
mesh_terms: D053299:Apolipoprotein B-100 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood* / Q000453:epidemiology / Q000209:etiology*; D048909:Diabetes Complications / Q000097:blood* / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011765:Pyruvaldehyde; D061205:Vascular Calcification / Q000097:blood* / Q000209:etiology*
chemical_list: D053299:Apolipoprotein B-100; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011765:Pyruvaldehyde