Int J Rheum Dis. 2026 Oct;29(10):e70910. doi: 10.1111/1756-185x.70910.
ABSTRACT
Antineutrophil cytoplasmic antibodies (ANCA) define a distinct group of small-vessel vasculitides collectively termed ANCA-associated vasculitis (AAV). Since their initial recognition as immunofluorescence patterns, ANCA have evolved into well-characterized pathogenic autoantibodies directed primarily against proteinase 3 (PR3) and myeloperoxidase (MPO). This review integrates the historical evolution of ANCA discovery with current understanding of disease pathogenesis and contemporary diagnostic practice. We summarize key biological mechanisms underlying AAV, including genetic susceptibility, epigenetic dysregulation, neutrophil priming, complement activation via the alternative pathway, and neutrophil extracellular trap formation, which together drive endothelial injury and necrotizing vasculitis. Recognition of PR3 ANCA and MPO ANCA as pathogenic entities has reshaped disease classification and supports the concept of biologically distinct disease subsets. In parallel, laboratory diagnostics have undergone a major paradigm shift. We critically review the transition from indirect immunofluorescence-first algorithms to immunoassay-first strategies endorsed by the 2017 revised international consensus, highlighting the improved diagnostic performance of contemporary antigen-specific immunoassays. The roles of automated immunofluorescence, biochip mosaic platforms, and multiparametric testing are discussed within harmonized diagnostic workflows. Emphasis is placed on strict clinical gating, quantitative antibody interpretation, and likelihood ratio-based reporting to enhance diagnostic accuracy and reduce false-positive results. By integrating historical, biological, and diagnostic perspectives, this review provides a practical reference framework for evidence-based ANCA testing and interpretation in clinical practice.
PMID:42858356 | DOI:10.1111/1756-185x.70910