Identification of immune responses against aldehyde-modified peptide sequences in apoB associated with cardiovascular disease.
OBJECTIVE
Atherosclerosis is associated with an immune response against oxidized LDL, which modulates the progression of the disease process.


RESULTS
Using a library of polypeptides covering the complete sequence of apoB-100, the only major protein of LDL, we have identified over 100 different human antibodies reacting against aldehyde-modified apoB-100 sequences. IgM antibody titer levels decreased with age and were associated with the intima-media thickness of the carotid artery in subjects younger than 60 years. There were also inverse associations between IgM levels and oxidized LDL in plasma. In prospective clinical studies, antibody levels against several aldehyde-modified apoB-100 sites were associated with cardiovascular disease in this age group. Whether this immune response is adaptive (protective) or maladaptive (causal) in atherosclerosis requires further investigation.


CONCLUSIONS
We have characterized a large number of epitopes within the apoB-100 component of oxidized LDL that provoke an immune response in humans. These findings will make it possible to study the role of immune responses against specific sites in oxidized LDL and to determine whether these immune responses influence the risk for future cardiac events.
Fredrikson
Gunilla Nordin
GN
Department of Medicine, Malmö University Hospital, Lund University, Malmö, Sweden. Gunilla.Nordin_Fredrikson@medforsk.mas.lu.se
Hedblad
Bo
B
Berglund
Göran
G
Alm
Ragnar
R
Ares
Mikko
M
Cercek
Bojan
B
Chyu
Kuang-Yuh
KY
Shah
Prediman K
PK
Nilsson
Jan
J
D000367:Age Factors; D000368:Aged; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D016893:Carotid Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006984:Hypertrophy; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000453:epidemiology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D019151:Peptide Library; D011446:Prospective Studies; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014463:Ultrasonography
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D019151:Peptide Library; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde