Abstract
The testing of anti-neutrophil cytoplasmic antibodies (ANCA) takes an important place in the diagnostic workup to ANCA-associated vasculitis (AAV). Nowadays, it is recommended to screen for the presence of PR3 and MPO specific antibodies first using immunoassay, without the need for ANCA measurement by indirect immunofluorescence (IIF). A literature search was performed to assess the diagnostic test value of ANCA IIF and PR3- and MPO-antibody immunoassay to diagnose AAV. This meta-analysis shows that the c-ANCA testing by IIF has a pooled sensitivity of 75.2% and a pooled specificity of 98.4%. For PR3-antibody immunoassay, the pooled sensitivity depended on the immunoassay method used, and ranged from 79.8% to 86.6%, whereas the pooled specificity ranged from 96.8% to 98.3%. For both p-ANCA IIF and MPO-antibody immunoassay (all methods) sensitivity varied considerably showing pooled values of respectively 46.3% and 58.1%, whereas respective pooled specificity was 91.4% and 95.6%. These findings support the 2017 international consensus that primary anti-PR3 and anti-MPO screening by immunoassay, based on superior immunoassay sensitivity without the need for IIF ANCA testing, improves the diagnostic workup of AAV.
Highlights
Antineutrophil cytoplasmic antibodies (ANCA) are antibodies that attack cytoplasmic components of neutrophils and monocytes [1]
A meta-analysis was done to estimate the sensitivity and specificity of can display a granular cyto plasmic pattern (c-ANCA) tested by indirect immunofluorescence and for the sensitivity and specificity of anti-proteinase 3 (PR3) tested by immunoassay
Sensitivity and specificity for c-ANCA in the previous study were comparable to the sensitivity and specificity in current meta-analysis
Summary
Antineutrophil cytoplasmic antibodies (ANCA) are antibodies that attack cytoplasmic components of neutrophils and monocytes [1]. In the 1999 international consensus statement, ANCA screening by indirect immunofluorescence (IIF) was recommended in suspected AAV and in case of ANCA IIF positivity, specific detection of PR3 and MPO antibodies was advised [21] This testing algorithm is still widely used, its diagnostic performance has recently been questioned. A more recent multicenter study showed that the diagnostic performance of current antigen-specific immunoassays equals or even exceeds the diagnostic performance of ANCA IIF to discriminate AAV from disease controls [22] These findings resulted in a new international consensus. We performed a systematic review and metaanalysis to evaluate the diagnostic value of ANCA testing using IIF and immunoassay (thereby comparing direct, capture and anchor immuno assay) in patients with AAV
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