Alpha 1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis

Kidney Int. 1993 Jun;43(6):1329-32. doi: 10.1038/ki.1993.186.


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.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies / blood*
  • Carboxypeptidases / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Pulmonary Emphysema / etiology
  • Vasculitis / enzymology*
  • Vasculitis / genetics
  • Vasculitis / immunology
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin Deficiency


  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies
  • alpha 1-Antitrypsin
  • Carboxypeptidases
  • proteinase C