Alpha 1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis.
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.
Esnault
V L
VL
Laboratoire d'Immunologie, Hotel Dieu, Nantes, France.
Testa
A
A
Audrain
M
M
Rogé
C
C
Hamidou
M
M
Barrier
J H
JH
Sesboüé
R
R
Martin
J P
JP
Lesavre
P
P
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
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D000515:alpha 1-Antitrypsin; D002268:Carboxypeptidases; C022471:proteinase C