Summary
Growing evidence indicates that elevated total homocysteine (tHcy) levels can elicit
autoimmune response in vivo. Antibodies against Nε-Hcy-proteins have been shown to be associated with stroke and premature myocardial
infarction. The aim of the current study was to investigate the effect of treatment
with folic acid on anti-Nε-Hcy-albumin and -hemoglobin antibodies. We recruited 20 apparently healthy men and
12 male patients with documented coronary artery disease (CAD). All participants had
plasma fasting tHcy levels >15 µM. At baseline, and after three and six months of
treatment with folic acid 1 mg daily, we determined tHcy, serum folate and vitamin
B12 levels, along with serum anti-Nε-Hcy-albumin and -hemoglobin IgG antibodies using the home-made immunoenzymatic assays.
Both groups did not differ with regard to age, tHcy, folate, lipid profile, and CRP.
The only significant difference between healthy subjects and CAD patients was levels
of antibodies against Nε-Hcy-albumin. As expected, folic acid administration led to significant decreases
in tHcy and increases in folate levels in both groups. Levels of both anti-Nε-Hcy-albumin and -hemoglobin antibodies fell markedly following a three-month folic
acid administration in healthy subjects, but not in CAD patients, without any changes
at six months in either group. Folic acid administration resulted in a loss of significant
correlations between tHcy and antibodies both following three and six months of the
therapy in healthy subjects, in contrast to CAD patients. Carriers of the methylenetetrahydrofolate
reductase (MTHFR) 677T allele with CAD had significantly higher levels of anti-Nε-Hcy-albumin before and during folic acid administration as compared to healthy subjects.
In conclusion, our findings suggest that Hcy-related autoimmune response is resistant
to folic acid administration in CAD patients, while in healthy subjects reduced tHcy
levels are associated with suppressed production of antibodies against Nε-Hcyproteins. These observations might explain at least in part the failure of vitamin
therapy to reduce the risk of cardiovascular events as recently reported.
Keywords
Arterial thrombosis - autoantibodies - homocysteine