Antineutrophil cytoplasmic antibody (ANCA) vasculitis: pathophysiology, diagnosis, and the evolving treatment landscape

The antineutrophil cytoplasmic antibody (ANCA) vasculitides include several closely related, often severe, multisystem autoimmune diseases characterized by antibodies against serine proteinase 3 (PR3) or myeloperoxidase. Loss of tolerance to these antigens triggers a cascade events, beginning with the priming neutrophils proinflammatory cytokines and complement activation, translocation ANCA-specific plasma membrane, neutrophil hyperactivation, further activation alternative pathway, leading tissue damage clinical manifestations ANCA vasculitis. Due heterogeneity in presentation diseases, diagnosis is substantially delayed, poor outcomes. current treatment pathway for most patients involves induction cyclophosphamide rituximab combination glucocorticoids, followed maintenance phase rituximab, azathioprine, methotrexate, during which time glucocorticoids are tapered. Current therapies effective inducing maintaining remission but associated range toxicities. Several new development Avacopan, an orally administered inhibitor fragment 5a (C5a) receptor, has been assessed trial may play role reducing cumulative glucocorticoid dose. Preliminary data suggest that cluster differentiation (CD) 80 CD86 blockade abatacept also have management There unmet need additional therapeutic options diseases.