Summary
N-homocysteinylated (Nε-Hcy) proteins and corresponding antibodies have recently been discovered in humans
and animals. Increased autoimmune response to Nε -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
Nε-Hcy-albumin were determined using an enzymelinked immunosorbent assay. Seropositivity
to anti-Nε -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 μ M vs 12.1 μ M; 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-Nε-Hcy-albumin antibodies and Hcy levels (r=0.16; p=0.03). By multivariate logistic
regression analysis, seropositivity to anti-Nε-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-Nε-Hcy-albumin antibodies were associated with C-reactive protein levels (r=0.24; p=0.002).
Seropositivity to anti-Nε-Hcy-albumin antibodies showed no association with the MTHFR C677T polymorphism.
Our results suggest that seropositivity to antibodies against Nε-homocysteinylated albumin is associated with early-onset CAD. An autoimmune response
to Nε-Hcy-albumin may represent a novel mechanism involved in the early development of
CAD.
Keywords
Antibodies - homocysteine - coronary artery disease