aetiology and pathogenesis of ANCA associated vasculitis

Last reviewed 09/2019

  • ANCA-Associated Vasculitis (AAV) are of unknown aetiology but generally considered to be autoimmune diseases due to the strong association with ANCA
    • evidence for an important genetic contribution to AAV has been growing, including a familial association
      • a genome-wide association study has confirmed that the pathogenesis of AAV has a genetic component, and that there are genetic distinctions between GPA (Wegeners) and MPA (microscopic polyangiitis) that are associated with ANCA specificity
        • PR3-ANCA was associated with HLA-DP, SERPINA1 (which encodes alpha1 antitrypsin, a serine proteinase inhibitor for which PR3 is one of several substrates) and PRTN3 (which encodes PR3), while MPO-ANCA was associated with HLA-DQ
        • ANCA are antibodies directed against neutrophil granule constituents
          • Two main patterns of staining are recognised using indirect immunofluorescence:
            • cytoplasmic (cANCA), a coarse granular staining of the cytoplasm, and perinuclear (pANCA), with staining chiefly around the nucleus, leaving the cytoplasm unstained
              • main target antigen for cANCA is serine PR3 located in azurophilic granules
            • main target for pANCA is MPO, an enzyme from azurophilic granules that catalyses peroxidation of chloride to hypochlorite
          • anti-PR3 antibodies are highly specific (>90%) for GPA
          • MPO antibodies are more typically found in MPA (microscopic polyangiitis) and EGPA (Churg-Strauss) but are much less specific
      • ANCA often correlate with disease activity, and there is increasing evidence to support their role in pathogenesis.


  • 1) ARC Autumn 2012. Topical Reviews - ANCA-associated vasculitis; 1:1-12.