title: Alpha 1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis.
abstract: Alpha 1-antitrypsin (alpha 1-AT) is the major inhibitor of proteinase 3 (PR3), the main target antigen of antineutrophil cytoplasm antibodies (ANCA) in Wegener's granulomatosis. alpha 1-AT is encoded by a polymorphic gene, with over 75 alleles, defining severely, medium and non-deficient protease inhibitor (PI) phenotypes. We describe the association of severely and medium deficient PI phenotypes with anti-PR3 positive systemic vasculitis, and postulate a pathogenetic role for alpha 1-AT deficiency and the occurrence of ANCA, with specificity for PR3 in a subgroup of patients with Wegener's granulomatosis.
authors.affiliation: Laboratoire d'Immunologie, Hotel Dieu, Nantes, France.
authors.forename: V L
authors.initials: VL
authors.lastname: Esnault
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.forename: M
authors.initials: M
authors.lastname: Audrain
authors.forename: C
authors.initials: C
authors.lastname: Rogé
authors.forename: M
authors.initials: M
authors.lastname: Hamidou
authors.forename: J H
authors.initials: JH
authors.lastname: Barrier
authors.forename: R
authors.initials: R
authors.lastname: Sesboüé
authors.forename: J P
authors.initials: JP
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Lesavre
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000097:blood*; D002268:Carboxypeptidases / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011656:Pulmonary Emphysema / Q000209:etiology; D014657:Vasculitis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D000515:alpha 1-Antitrypsin; D002268:Carboxypeptidases; C022471:proteinase C