title: 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.
authors.affiliation: Division of Nephrology, San Carlo Borromeo Hospital, Milan, Italy. a.fornasieri@oscb.sined.net
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fornasieri
authors.forename: Cristina
authors.initials: C
authors.lastname: Perugini
authors.forename: Milfred
authors.initials: M
authors.lastname: Seccia
authors.forename: Pietro
authors.initials: P
authors.lastname: Napodano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Amico
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000276:immunology*; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000276:immunology*; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein