Anti-oxidized low-density lipoprotein antibodies in myeloperoxidase-positive vasculitis patients preferentially recognize hypochlorite-modified low density lipoproteins

Clin Exp Immunol. 2007 Aug;149(2):257-64. doi: 10.1111/j.1365-2249.2007.03420.x. Epub 2007 May 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / analysis
  • Autoantibodies / blood*
  • Autoimmune Diseases / enzymology
  • Autoimmune Diseases / immunology*
  • Copper
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Glomerulonephritis / enzymology
  • Glomerulonephritis / immunology
  • Humans
  • Hypochlorous Acid
  • Lipoproteins, LDL / immunology*
  • Male
  • Malondialdehyde
  • Middle Aged
  • Oxidation-Reduction
  • Peroxidase / metabolism*
  • Renal Dialysis
  • Vasculitis / enzymology
  • Vasculitis / immunology*

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Malondialdehyde
  • Hypochlorous Acid
  • Copper
  • Peroxidase