Diagnostic ANCA algorithms in daily clinical practice: evidence, experience, and effectiveness

Detection of antineutrophil cytoplasmic antibodies (ANCA) for ANCA-associated vasculitides (AAV) is based on indirect immunofluorescence (IIF) on ethanol-fixed neutrophils and reactivity toward myeloperoxidase (MPO) and proteinase 3 (PR3). According to the international consensus for ANCA testing, presence of ANCA should at least be screened for by IIF and, if positive, followed by antigen-specific immunoassays. Optimally, all samples are analyzed by both IIF and quantitative antigen-specific immunoassays. Since the establishment of this consensus many new technologies have become available and this has challenged the positioning of IIF in the testing algorithm for AAV. In the current paper, we summarize the novelties in ANCA diagnostics and discuss the possible implications of these developments for the different ANCA algorithms that are currently applied in routine diagnostic laboratories. Possible consequences of replacing ANCA assays by novel methods are illustrated by our data obtained in daily clinical practice. Eventually, it is questioned if there is a need to change the consensus, and if so, whether IIF can be discarded completely, or be used as a confirmation assay instead of a screening assay. Both alternative options require that ANCA requests for AAV can be separated from ANCA requests for gastrointestinal autoimmune diseases.