title: Inhibition of oxidation activity of myeloperoxidase (MPO) by propylthiouracil (PTU) and anti-MPO antibodies from patients with PTU-induced vasculitis.
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.
authors.affiliation: Renal Division and Institute of Nephrology, Peking University First Hospital, Beijing 100034, PR China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000502:physiology*; D000963:Antimetabolites / Q000009:adverse effects*; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000201:enzymology / Q000276:immunology; D000882:Haplorhini; D006801:Humans; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology; D010084:Oxidation-Reduction / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D011441:Propylthiouracil / Q000009:adverse effects*; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000963:Antimetabolites; D011441:Propylthiouracil; D009195:Peroxidase; D053146:Myeloblastin