Autoimmun Rev. 2026 Jul 21:104143. doi: 10.1016/j.autrev.2026.104143. Online ahead of print.

ABSTRACT

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a group of rare, potentially life-threatening autoimmune disorders characterized by necrotizing inflammation of small vessels. Over recent decades, remarkable advances have been made in unraveling its immunopathogenesis, emphasizing the interplay between genetic predisposition, environmental triggers, loss of immune tolerance, neutrophil extracellular trap formation, and complement-mediated neutrophil activation. This review provides an integrative synthesis of recent mechanistic and clinical insights into AAV, bridging fundamental immunology with translational and therapeutic advances. Based on an extensive literature search of PubMed and Scopus, studies were selected according to methodological quality and clinical relevance. Distinct ANCA specificities, proteinase 3 (PR3) and myeloperoxidase (MPO), define overlapping yet prognostically divergent subsets, with PR3-ANCA linked to relapsing multisystem disease and MPO-ANCA to renal involvement and progression to kidney failure. Therapeutic paradigms have evolved from cyclophosphamide-based induction toward rituximab-centered and glucocorticoid-sparing regimens, with avacopan and mepolizumab further improving efficacy and safety profiles. Despite five-year survival rates exceeding 85%, long-term morbidity persists, driven by relapse and treatment-related toxicity. However, precision therapy in AAV remains incomplete, as current treatment selection is still guided mainly by disease severity, organ involvement, relapse risk, comorbidities, renal histology, and glucocorticoid-toxicity risk rather than by validated molecular biomarkers. Emerging data on complement activation, urinary inflammatory biomarkers, B-cell kinetics, and tissue-based transcriptomic profiling may refine disease endotyping and individualized monitoring. Collectively, these advances herald a transition from empirical immunosuppression toward biologically informed, precision-oriented care in vasculitis.

PMID:42480954 | DOI:10.1016/j.autrev.2026.104143