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.
Undas
Anetta
A
Institute of Cardiology, Jagiellonian University School of Medicine, 80 Pradnicka Street, 31-202 Cracow, Poland. mmundas@cyf-kr.edu.pl
Kolarz
Marek
M
Kopec
Grzegorz
G
Glowacki
Rafal
R
Placzkiewicz-Jankowska
Ewa
E
Tracz
Wiesława
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D003324:Coronary Artery Disease / Q000209:etiology / Q000276:immunology; D005260:Female; D006454:Hemoglobins / Q000276:immunology* / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000276:immunology; D006435:Renal Dialysis / Q000009:adverse effects*; D012709:Serum Albumin / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D001323:Autoantibodies; D006454:Hemoglobins; C502359:N-homocysteinylated albumin; D012709:Serum Albumin; D006710:Homocysteine