Immunoglobulins against tyrosine-nitrated epitopes in coronary artery disease.
BACKGROUND
Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine-nitrated proteins, a footprint of oxygen- and nitrogen-derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of patients with coronary artery disease (CAD). However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored.


RESULTS
Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of patients with CAD. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in patients with CAD (n=374) and subjects without CAD (non-CAD controls, n=313). A 10-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in patients with CAD (3.75±1.8 μg antibody Eq/mL plasma versus 0.36±0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD.


CONCLUSIONS
The results of this cross-sectional study suggest that posttranslational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neo-epitopes for the elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD.
Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104-4318, USA.
Leonor
L
Thomson
Margarita
M
Tenopoulou
Richard
R
Lightfoot
Epida
E
Tsika
Ioannis
I
Parastatidis
Marissa
M
Martinez
Todd M
TM
Greco
Paschalis-Thomas
PT
Doulias
Yuping
Y
Wu
W H Wilson
WH
Tang
Stanley L
SL
Hazen
Harry
H
Ischiropoulos
D000368:Aged; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology*; D003430:Cross-Sectional Studies; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007107:Immune System / Q000503:physiopathology; D007136:Immunoglobulins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology
D000939:Epitopes; D007136:Immunoglobulins; C002744:3-nitrotyrosine; D014443:Tyrosine