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.