ANCA-associated vasculitis: is there a role for neutrophil apoptosis in autoimmunity?

Abstract

The primary small vessel systemic vasculitides are disorders that target small blood vessels, inducing vessel wall inflammation, and are associated with the development of antineutrophil cytoplasmic antibodies. Multiple organs are attacked including the lungs and kidneys. Increasing knowledge of pathogenesis suggests that the antibodies activate neutrophils inappropriately, leading to endothelial and vascular damage. Cytokines, such as tumor necrosis factor, can facilitate damage by priming neutrophils and activating endothelial cells. Apoptosis of infiltrating neutrophils is also disrupted by antineutrophil cytoplasmic antibody activation. Removal of these effete cells occurs in a proinflammatory manner, promoting persistent inflammation. The autoimmune response may be promoted by aberrant phagocytosis of apoptotic neutrophils by dendritic cells. Understanding pathogenesis can help to rationalize existing therapies and indicate new approaches to therapy.