Circulating antibodies recognizing malondialdehyde-modified proteins in healthy subjects.
Antibodies against malondialdehyde (MDA)-modified proteins are often increased in patients with diseases related to oxidative stress. However, the clinical significance of these antibodies is hampered by their frequent presence also in healthy controls. Aim of this work has been to characterize the immune reactivity against MDA-derived antigens in healthy subjects. The sera of 120 healthy subjects contained IgG and IgM targeting MDA-modified human albumin (HSA), fibrinogen, and LDL. These sera also displayed weak reactivity with oxidized LDL and HSA complexed with oxidized arachidonic acid. Conversely, oxidized HSA or HSA complexed with other aldehydic lipid peroxidation products was not recognized. Control sera also did not recognize cyclic dihydropyridine-MDA products, while HSA-MDA reactivity was associated (r > 0.9; p <.0005) with the presence of fluorescent lysine-conjugated-imine cross-links. In Western blots both IgG and IgM recognized high molecular weight HSA-MDA aggregates, but not monomeric HSA-MDA adducts. The addition of sodium cyanoborohydride, that prevented conjugated-imine fluorescence and protein aggregation during HSA-MDA preparation, abolished the antibody binding. This suggested that the plasma of healthy subjects contained IgG and IgM recognizing protein aggregates linked through 1-amino-3-imino-propene bridges. The function of these antibodies is at the moment unknown, but they might contribute to scavenging MDA cross-linked proteins.
Vay
D
D
Department of Medical Sciences, University Amedeo Avogadro of East Piedmont, Via Solaroli 17, 28100 Novara, Italy.
Parodi
M
M
Rolla
R
R
Mottaran
E
E
Vidali
M
M
Bellomo
G
G
Albano
E
E
D000328:Adult; D016718:Arachidonic Acid / Q000737:chemistry / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D001798:Blood Proteins / Q000737:chemistry* / Q000276:immunology*; D015153:Blotting, Western; D005260:Female; D005340:Fibrinogen / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry* / Q000276:immunology*; D008875:Middle Aged; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D001798:Blood Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D012709:Serum Albumin; C099252:oxidized low density lipoprotein; D016718:Arachidonic Acid; D008315:Malondialdehyde; D005340:Fibrinogen