Autoantibodies against N-homocysteinylated proteins in patients on long-term haemodialysis.

BACKGROUND

Autoantibodies against N(epsilon)-homocysteinylated (N(epsilon)-Hcy) proteins at high titres have been demonstrated in patients with premature coronary artery disease (CAD) and stroke. Since recently, elevated N(epsilon)-Hcy-proteins levels have been reported in haemodialysis patients, we sought to investigate whether anti-N(epsilon)-Hcy-protein antibodies occur in such subjects and if they are associated with cardiovascular risk.

METHODS

We studied 43 patients, aged 27-89 (mean 58.8) years, dialysed for, on average, 50 months and 31 age- and sex-matched healthy controls. IgG antibodies against N(epsilon)-Hcy-albumin and -haemoglobin were determined using an in-house enzyme-linked immunosorbent assay.

RESULTS

Haemodialysis patients had higher plasma tHcy (23.18 +/- 1.37 vs 13.51 +/- 0.64; P < 0.0001), serum folate (29.7 +/- 6.9 vs 9.9 +/- 3.8 nmol/l; P < 0.0001) and anti-N(epsilon)-Hcy-albumin and -haemoglobin antibodies (absorbancy at 490 nm: 0.39 +/- 0.22 vs 0.34 +/- 0.12; P = 0.03 and 0.60 +/- 0.31 vs 0.42 +/- 0.09; P < 0.0001, respectively) than controls. Levels of anti-N(epsilon)-Hcy-albumin antibodies, but not those against haemoglobin, correlated negatively with the duration of haemodialysis (r = -0.39; P = 0.01). This correlation disappeared after a 6-month follow-up. Haemodialysis patients treated with folic acid on a long-term basis had similar levels of anti-N(epsilon)-Hcy-albumin and -haemoglobin antibodies compared with the minority which denied taking this vitamin (absorbancy A490: 0.35 +/- 0.22 vs 0.38 +/- 0.05; P = 0.5 and 0.63 +/- 0.30 vs 0.51 +/- 0.11; P = 0.4, respectively).

CONCLUSIONS

Our study shows that an autoimmune response to anti-N(epsilon)-Hcy-proteins occurs in patients on maintenance haemodialysis and is more pronounced than in healthy subjects.