Antibodies against N‑homocysteinylated proteins and their determinants in patients on long‑term hemodialysis

INTRODUCTION: The factors that determine the level of antibodies against N‑homocysteinylated (N‑Hcy) proteins have not been established so far. The clinical significance of these antibodies and their effect on cardiovascular (CV) risk in patients with end‑stage renal disease (ESRD) are still unknown. OBJECTIVES: The aim of this study was to identify the factors that determine the level of antibodies against N‑Hcyalbumin and N‑Hcy hemoglobin in patients on long‑term hemodialysis (HD). PATIENTS AND METHODS: The study involved 247 subjects on long-term HD (110 women, 137 men; age range, 23–89 years) and 60 controls matched for age, sex, and CV risk factors (serum creatinine level <140 μmol/l). Serum antibodies against N‑Hcyalbumin and N‑Hcyhemoglobin were determined using an in‑house enzyme‑linked immunosorbent assay. Total homocysteine (tHcy), folate, and 8‑isoprostaglandin F2α (8‑iso‑PGF 2α) were also measured. RESULTS: Patients on HD had higher serum levels of anti‑N‑Hcy‑albumin (absorbancy at 490 nm: 0.56 [0.49–0.623] vs. 0.259 [0.198–0.338], P <0.0001) and anti‑N‑Hcy‑hemoglobin antibodies (0.659 [0.597–0.723] vs. 0.379 [0.289–0.442], P <0.0001) as compared with controls. The level of both antibodies correlated with tHcy (r = 0.56, P <0.0001 and r = 0.67, P <0.0001, respectively), 8‑iso‑PGF 2α (r = 0.48, P <0.0001 and r = 0.63, P <0.0001, respectively), and folate (r = –0.18, P = 0.0054 and r = –0.38, P <0.0001, respectively), but not with HD duration, the initial cause of ESRD, and CV comorbidity. CONCLUSIONS: In HD patients, tHcy is an independent predictor of antibodies against N‑Hcy proteins. Folate and 8‑iso‑PGF 2α concentrations were not independently associated with the levels of both antibodies.