Pathogenesis of ANCA-associated vasculitis

Abstract

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises a group of systemic inflammatory vasculitides associated with circulating autoantibodies directed against the neutrophil granule components proteinase 3 and myeloperoxidase. ANCA interact with their target antigens on cytokine primed neutrophils, causing neutrophil activation via several signaling pathways that culminates in endothelial interaction, degranulation, cytokine production, and endothelial and tissue damage. The presence of autoantibodies implies the assistance of autoreactive T-helper cells and B cells, and a failure of regulatory mechanisms. This article reviews the current evidence for the pathogenic mechanisms culminating in autoantibody production, the effects of ANCA-neutrophil and neutrophil-endothelial interactions, and the mechanisms of tissue damage.