Performance of MPO-ANCA and PR3-ANCA immunoassays for the stratification of specific ANCA-associated vasculitis: A systematic review and meta-analysis

To determine the impact of myeloperoxidase (MPO) and proteinase 3 (PR3) antigen-specific immunoassays in the stratification of patients at-risk for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) at diagnosis.A Medline search was conducted to identify diagnostic accuracy studies using PR3-ANCA or MPO-ANCA for the evaluation of granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies estimates were pooled using the bivariate method.Diagnostic accuracy varied by analyte and AAV subtype. PR3-ANCA had greater sensitivity than MPO-ANCA for GPA (74% vs 11%, p < 0.001) and MPO-ANCA greater sensitivity for MPA (73% vs 7%, p < 0.001). Specificities of both MPO-ANCA and PR3-ANCA were consistently high (mean 97%, range: 93-99%) for both AAV subtypes. There was insufficient data to perform meta-analysis for the diagnostic accuracy of EPGA.These results validate the use of high quality MPO-ANCA and PR3-ANCA immunoassays to screen patients at-risk for AAV as well as to categorize disease as GPA or MPA subtype. However, caution must be exercised in doing so, since some assays may not have optimal performance. Each laboratory should validate appropriate algorithms based on the tests used and testing population.