Humoral immune response against defined oxidized low-density lipoprotein antigens reflects structure and disease activity of carotid plaques.
BACKGROUND
Immune responses against oxidized low-density lipoprotein (LDL) play an important role in atherosclerosis. The aim of this study was to investigate if humoral immune response against specific oxidized LDL antigens, such as aldehyde-modified peptide sequences of apolipoprotein B-100, reflects disease activity and structure of atherosclerotic plaques.


RESULTS
Plaques were obtained from 114 symptomatic subjects referred to carotid endarterectomy and characterized immunohistochemically and histologically. Plasma levels of IgG and IgM against aldehyde-modified apolipoprotein B-100 amino acid sequences 661 to 680, 3136 to 3155 (peptide 210), and 3661 to 3680 (peptide 240) were determined by enzyme-linked immunosorbent assay. High levels of IgG against peptide 210 were associated with increased plaque content of lipids (r=0.24, P<0.05) and hemorrhage (r=0.27, P=0.005), with decreased content of fibrous tissue (r=-0.25, P=0.01), but also with lower total plaque volume (r=-0.21, P<0.05). In contrast, high levels of IgM against peptide 240 were associated with plaques with more fibrous tissue (r=0.35, P<0.001), less lipids (r=-0.34, P<0.001), and less macrophages (r=-0.24, P<0.05). IgM against peptide 210 were found to be associated with plaque fibrous tissue (r=0.20, P<0.05), less lipids (r=-0.21, P<0.05), and less macrophages (r=-0.27, P=0.01).


CONCLUSIONS
These findings support the notion that immune responses against oxidized LDL epitopes are involved in atherosclerosis and that the level of circulating antibodies against these structures may reflect disease activity in the arterial wall.
Gonçalves
Isabel
I
Department of Medicine, Lund University, Wallenberg Laboratory, University Hospital MAS, Malmö, Sweden. isabel.goncalves@medforsk.mas.lu.se
Gronholdt
Marie-Louise M
ML
Söderberg
Ingrid
I
Ares
Mikko P S
MP
Nordestgaard
Borge G
BG
Bentzon
Jacob F
JF
Fredrikson
Gunilla Nordin
GN
Nilsson
Jan
J
D000368:Aged; D000917:Antibody Formation / Q000276:immunology*; D001158:Arteries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002340:Carotid Artery Diseases / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein