Inhibition of oxidation activity of myeloperoxidase (MPO) by propylthiouracil (PTU) and anti-MPO antibodies from patients with PTU-induced vasculitis

Clin Immunol. 2007 Feb;122(2):187-93. doi: 10.1016/j.clim.2006.09.011. Epub 2006 Oct 27.

Abstract

Propylthiouracil (PTU) could induce antineutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study aimed to investigate the inhibitory effects on MPO oxidation activity by PTU and MPO-ANCA from patients with primary microscopic polyangiitis (MPA) and PTU-induced vasculitis. IgG preparations were purified from MPO-ANCA-positive sera from seven patients with PTU-induced vasculitis and ten patients with primary MPA. The oxidation activity of MPO was measured in the presence of PTU and MPO-ANCA-positive IgG preparations from patients with PTU-induced vasculitis and primary MPA respectively. PTU could competitively inhibit the oxidation activity of MPO dose dependently. MPO-ANCA-positive IgG preparations from 6/7 patients with PTU-induced vasculitis and only 3/10 from patients with primary MPA could inhibit the MPO activity in a dose-dependent manner. In conclusions, the oxidation activity of MPO could be inhibited by PTU and PTU-induced MPO-ANCA in a dose-dependent manner, which might be involved in the pathogenesis PTU-induced vasculitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Antineutrophil Cytoplasmic / physiology*
  • Antimetabolites / adverse effects*
  • Female
  • Granulomatosis with Polyangiitis / enzymology
  • Granulomatosis with Polyangiitis / immunology
  • Haplorhini
  • Humans
  • Male
  • Middle Aged
  • Myeloblastin / immunology
  • Oxidation-Reduction / drug effects
  • Peroxidase / antagonists & inhibitors*
  • Peroxidase / immunology*
  • Peroxidase / metabolism
  • Propylthiouracil / adverse effects*
  • Vasculitis, Leukocytoclastic, Cutaneous / chemically induced
  • Vasculitis, Leukocytoclastic, Cutaneous / enzymology
  • Vasculitis, Leukocytoclastic, Cutaneous / immunology*

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Antimetabolites
  • Propylthiouracil
  • Peroxidase
  • Myeloblastin