Antineutrophil Cytoplasmic Antibodies with Specificity for Proteinase 3

Antineutrophil cytoplasmic antibodies (ANCA) with specificity for proteinase 3 (PR3-ANCA) are valuable serological markers for entities termed "ANCA-associated vasculitides" (AAV: granulomatosis with polyangiitis "Wegener" (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg Strauss syndrome) and, in particular, for GPA. Consensus guidelines currently recommend performing indirect immunofluorescence (IIF) testing together with an enzyme-linked immunosorbent assay (ELISA) (or other immunometric assays) to detect PR3-ANCA. Generally, antibodies to PR3 give a cytoplasmic staining (C-ANCA) on ethanol-fixed neutrophils and the specific antigen is usually detected by different ELISAs (. direct, capture, and anchor). The prevalence of PR3-ANCA is between 60% and 97% in GPA, and is much lower in MPA and EGPA. However, PR3-ANCA have also been observed in other disorders, such as ulcerative colitis, infectious disorders (i.e., subacute bacterial endocarditis), drug-induced syndrome (i.e., cocaine-induced midline destructive lesions), and other disorders not associated with vascular inflammation. In general, PR3-ANCA levels are useful to monitor disease activity but should not be used by themselves to guide treatments. A genome-wide association study (GWAS) in AAV confirms a genetic component to AAV pathogenesis, demonstrates genetic distinctions between GPA and MPA that are associated with ANCA specificity, and suggests that the response against the autoantigen PR3 is a central pathogenic feature of PR3-ANCA-associated vasculitis.