Circulating antibodies recognising oxidatively-modified low-density lipoproteins in patients with IgA nephropathy, membranous glomerulonephritis and focal glomerulosclerosis

Abstract

Background: Oxidation of low-density lipoproteins (LDL) generates molecular epitopes that play a pathologic role in experimental glomerular diseases and can also elicit an immune response and the generation of anti-oxidatively-modified LDL antibodies.

Methods: We investigated, for the first time in humans, the enhanced induction of LDL oxidation in chronic glomerulonephritis, the presence of circulating antibodies against oxidatively-modified LDL in patients with IgA glomerulonephritis (IgA GN) or with nephrotic syndrome associated with focal glomerulosclerosis (FGS) and primary membranous glomerulonephritis (MGN). The antibody levels were measured by enzyme-linked immunosorbent assay (ELISA) using native and copper-, peroxidase-, hypochlorite-, and peroxynitrite-oxidized LDL.

Results: Compared to control subjects, the three groups of patients, particularly the IgA GN patients, had higher serum levels of antibodies recognising LDL oxidised with the four different modalities and higher concentrations of cholesterol in circulating immune complexes. None of these were significantly correlated with any demographic, histological or biochemical laboratory finding. In patients with IgAGN, we investigated the possible confounding effects of cardiovascular risk factors (hypercholesterolemia, hypertension, diabetes and overt atherosclerosis). Although the concentration of cholesterol in circulating immune complexes was significantly higher in patients with cardiovascular risk factors, no significant differences were observed in the level of anti-oxidised-LDL antibodies. This analysis, however, was impossible in FGS and MGN patients because of the high prevalence of hypercholesterolemia in these groups.

Conclusions: These results suggest that IgA GN, MGN and FGS are associated with an enhanced immune response to LDL oxidised with different stimuli mimicking the pro-oxidant environment occurring in vivo, mirrored by the increased levels of specific antibodies, very likely linked to enhanced in vivo LDL oxidation which might participate in glomerular damage and progression.