Autoantibodies against oxidatively-modified LDL in uremic patients undergoing dialysis

Target-specific oxidation processes in LDL generate molecular epitopes that are more atherogenic than the native forms and are able to elicit an immunological reaction leading to the formation of anti-oxLDL autoantibodies (oxLDL-Ab) that may participate in the overall process of atherogenesis. Thus, the detection of oxLDLAb, in addition to mirroring the occurrence of in vivo LDL oxidation, will give valuable information on the occurrence of this immune response. Plasma oxLDLAb (IgG and IgM) were measured in 72 control subjects (CS) and in 80 patients with chronic renal failure (CRF), undergoing repetitive hemodialysis (N = 56) or peritoneal dialysis (N = 24), with an ELISA method using native LDL, CuSO₄-oxidized LDL (oxLDL) or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross reactivity of the antibodies detected with other oxidatively-modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed as antigens. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins. CRF patients had an antibody ratio significantly higher than CS as concerning anti-oxLDL IgG (1.39 ± 0.36 vs. 1.05 ± 0.3, P < 0.05) and IgM (2.15 ± 0.75 vs. 1.43 ± 0.43, P < 0.01), and anti-MDA-LDL IgG (3.05 ± 0.74 vs. 2.04 ± 0.42, P < 0.01) and IgM (5.55 ± 1.79 vs. 2.9 ± 0.85, P < 0.01). The anti-MDA-HSA antibody titer was also higher in CRF patients than in CS (2.49 ± 0.5 vs. 1.46 ± 0.39, P < 0.01 for IgG and 2.80 ± 1.03 vs. 1.26 ± 0.43, P < 0.01 for IgM). Subclass analysis regarding the type of dialytic treatment revealed that the autoantibody pattern did not differ between CRF patients on hemodialysis and peritoneal dialysis. However, the ratio between anti-MDA-LDL and anti-MDA-HSA (a parameter indicating the specificity of LDL over albumin as the molecule triggering the immunological response) was higher in CRF patients on hemodialysis as compared to peritoneal dialysis (1.34 ± 0.43 vs. 1.12 ± 0.29, P < 0.05 for IgG and 2.41 ± 1.22 vs. 1.75 ± 0.78, P < 0.01 for IgM). Furthermore, 10% of CRF patients had detectable levels of immune complexes containing oxidized LDL and IgG. These data indicate that CRF patients on dialytic treatment, and particularly on hemodialysis, develop autoantibodies against oxidatively-modified LDL and support the occurrence of an enhanced LDL oxidation in vivo.