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.
Reference:
Mahr A et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etiopathogenesis, assessment and management. Curr Opin Rheumatol. 2014 Jan;26(1):16-23.
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