title: Anti-oxidized low-density lipoprotein antibodies in myeloperoxidase-positive vasculitis patients preferentially recognize hypochlorite-modified low density lipoproteins.
abstract: Many patients surviving vasculitis are prone to accelerated atherosclerosis and often have enhanced levels of antibodies to oxidized low-density lipoprotein (oxLDL). To measure anti-oxLDL antibodies, oxidation of LDL is achieved with copper (Cu) or malondialdehyde (MDA). Because, in vivo, LDL may be oxidized with myeloperoxidase (MPO) or its product hypochlorite, we measured anti-hypochlorite LDL antibodies in patients with vasculitis, haemodialysis patients and healthy controls. A newly developed enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to oxLDL as modified by hypochlorite. Results are compared with data obtained by standard LDL oxidation using MDA-LDL or Cu-LDL as substrate. Results were compared between anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients (n = 93), haemodialysis (HD) patients (n = 59) and healthy controls (HC; n = 43). Furthermore, patients with MPO-ANCA-associated vasculitis (n = 47) were compared with patients with proteinase 3 (PR3)-ANCA associated vasculitis (n = 46). Optimal cut-off points were determined by receiver operator characteristic (ROC) curve analysis. Anti-oxLDL antibodies are enhanced in AAV patients (MDA-LDL and hypochlorite-LDL) and in HD patients (hypochlorite-LDL), when compared to HC. Furthermore, patients with MPO-ANCA-associated vasculitis had higher levels of antibodies to hypochlorite-LDL than patients with PR3-ANCA-associated vasculitis. Our newly developed assay, in which hypochlorite-LDL is used as substrate, seems a more sensitive assay than traditional assays to measure oxLDL antibodies. Furthermore, our results suggest that enhanced MPO-mediated LDL oxidation occurs in patients with MPO-ANCA.
authors.affiliation: Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Slot
authors.forename: R
authors.initials: R
authors.lastname: Theunissen
authors.forename: P
authors.initials: P
authors.lastname: van Paassen
authors.forename: J G M C
authors.initials: JG
authors.lastname: Damoiseaux
authors.forename: J W Cohen
authors.initials: JW
authors.lastname: Tervaert
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology*; D003300:Copper; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005921:Glomerulonephritis / Q000201:enzymology / Q000276:immunology; D006801:Humans; D006997:Hypochlorous Acid; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D008315:Malondialdehyde; D008875:Middle Aged; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D006435:Renal Dialysis; D014657:Vasculitis / Q000201:enzymology / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D006997:Hypochlorous Acid; D003300:Copper; D009195:Peroxidase