Pathogenesis of ANCA-associated vasculitis: new possibilities for intervention

Am J Kidney Dis. 2013 Dec;62(6):1176-87. doi: 10.1053/j.ajkd.2013.05.009. Epub 2013 Jun 28.


The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) comprise granulomatosis with polyangiitis (GPA), primarily associated with antibodies to proteinase 3 (PR3-ANCA); microscopic polyangiitis (MPA); and eosinophilic granulomatosis with polyangiitis (EGPA), both principally associated with antibodies to myeloperoxidase (MPO-ANCA). Genetic and environmental factors are involved in their etiopathogenesis, with a possible role for silica exposure in AAVs and Staphylococcus aureus infection in GPA. The distinct associations of PR3-ANCA and MPO-ANCA with different HLA class II antigens, which are stronger than those with the associated diseases, suggest a pathogenic role for those ANCAs and indicate that GPA and MPA are different diseases. Both in vitro and in vivo experimental data have shown that MPO-ANCA can induce necrotizing small-vessel vasculitis and glomerulonephritis. The additional role of the alternative pathway of complement activation has been demonstrated in human and experimental pathology. Also, T cells seem to be involved in lesion development, particularly in the kidney. Granuloma formation, as seen in PR3-ANCA-associated GPA, is not well explained by the presence of autoantibodies in experimental models. Here, T cells seem crucial. Recently obtained insights into the pathogenesis of AAVs have led to more targeted treatment of these life-threatening diseases.

Keywords: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis; antibodies to myeloperoxidase (MPO-ANCA); antibodies to proteinase 3 (PR3-ANCA); granulomatosis with polyangiitis (GPA); microscopic polyangiitis (MPA); pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / genetics*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology
  • Churg-Strauss Syndrome / genetics*
  • Churg-Strauss Syndrome / immunology
  • Complement Pathway, Alternative / genetics
  • Complement Pathway, Alternative / immunology
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease / genetics
  • Glomerulonephritis / genetics
  • Glomerulonephritis / immunology
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Microscopic Polyangiitis / genetics*
  • Microscopic Polyangiitis / immunology
  • Myeloblastin / immunology
  • Peroxidase / genetics*
  • Peroxidase / immunology
  • Polyarteritis Nodosa / genetics
  • Polyarteritis Nodosa / immunology
  • Silicon Dioxide / adverse effects
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / genetics
  • T-Lymphocytes / immunology


  • Histocompatibility Antigens Class II
  • Silicon Dioxide
  • Peroxidase
  • Myeloblastin