Antibodies to N-homocysteinylated albumin as a marker for early-onset coronary artery disease in men.
N-homocysteinylated (Nepsilon-Hcy) proteins and corresponding antibodies have recently been discovered in humans and animals. Increased autoimmune response to Nepsilon-Hcy-proteins has been reported in stroke patients. The aim of the present study was to investigate whether antibodies against N-homocysteinylated albumin are associated with coronary artery disease (CAD). We studied 88 male patients aged 50 years or under with angiographically documented CAD and 100 age-matched apparently healthy men as controls. Serum levels of IgG antibodies against Nepsilon-Hcy-albumin were determined using an enzymelinked immunosorbent assay. Seropositivity to anti-Nepsilon-Hcy-albumin antibodies was 5-fold more frequent in CAD patients than in controls (52.3% vs 10.0%; p<0.0001). Plasma Hcy levels in CAD patients were also significantly higher in the former than in the latter group (medians, 13.0 microM vs 12.1 microM; p=0.026). Importantly, 41.2% of subjects with plasma total Hcy >14.5 mM were seropositive compared with 25.5% of normohomocysteinemic individuals (p=0.048). There was a weak correlation between anti-Nepsilon-Hcy-albumin antibodies and Hcy levels (r=0.16; p=0.03). By multivariate logistic regression analysis, seropositivity to anti-Nepsilon-Hcy-albumin antibodies was an independent predictor of early CAD (OR, 14.82; 95% CI, 4.47 to 49.19; p=0.00002). Interestingly, anti-Nepsilon-Hcy-albumin antibodies were associated with C-reactive protein levels (r=0.24; p=0.002). Seropositivity to anti-Nepsilon-Hcy-albumin antibodies showed no association with the MTHFR C677T polymorphism. Our results suggest that seropositivity to antibodies against Nepsilon-homocysteinylated albumin is associated with early-onset CAD. An autoimmune response to Nepsilon-Hcy-albumin may represent a novel mechanism involved in the early development of CAD.
Undas
Anetta
A
Department of Medicine, Jagiellonian University School of Medicine, 8 Skawinska Street, 31-066 Cracow, Poland.
Jankowski
Milosz
M
Twardowska
Magdalena
M
Padjas
Agnieszka
A
Jakubowski
Hieronim
H
Szczeklik
Andrzej
A
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000097:blood*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012709:Serum Albumin / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; C502359:N-homocysteinylated albumin; D012709:Serum Albumin; D006710:Homocysteine