title: Alpha-1-antitrypsin phenotyping in ANCA-associated diseases: one of several arguments for protease/antiprotease imbalance in systemic vasculitis.
abstract: The vasculitic lesions observed in Wegener's granulomatosis may be partly the consequence of proteases released following activation of neutrophils by ANCA. The activity of these proteases, including proteinase 3 (PR3) and elastase, is normally closely restricted to the inflammation site by a large excess of circulating alpha-1-antitrypsin (alpha1AT). Patients with ANCA-positive systemic vasculitis may exhibit a protease/antiprotease imbalance either genetically determined in the rare patients with deficient alpha1AT phenotypes, or more often acquired through both alpha1AT inactivation in various pathological conditions and possible inhibition of PR3/alpha1AT complexation by anti-PR3 ANCA. This imbalance may at least contribute to disease spreading or aggravation.
authors.affiliation: Service de Néphrologie-Immunologie clinique, CHU Hôtel-Dieu, Nantes, France. vesnault@nantes.inserm.fr
authors.forename: V L
authors.initials: VL
authors.lastname: Esnault
authors.forename: M A
authors.initials: MA
authors.lastname: Audrain
authors.forename: R
authors.initials: R
authors.lastname: Sesboüé
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000276:immunology*; D014657:Vasculitis / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001324:Autoantigens; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D012697:Serine Endopeptidases