The role of neutrophils in ANCA-associated vasculitis

• Neutrophils are central to the pathogenesis of anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV) as they are both the target of the autoantibody and mediators of vascular injury. • There is good evidence for the pathogenicity of ANCA from in clinical, In vitro and in vivo studies. • ANCA activation of neutrophils leads to a range of pathogenic responses including ROS production, NETosis, cytokine release, and complement activation. • Neutrophil cross-talk with other cells of the adaptive and innate immune system amplifies vascular injury, and the autoimmune response in AAV. • Neutrophils are increasingly recognised to be heterogenous and neutrophils subsets with distinct functional characteristics may play a role in the pathogenesis on AAV. Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of rare systemic autoimmune diseases characterised by necrotising inflammation of small blood vessels and usually associated with circulating ANCA. The pathophysiology of AAV is complex, involving many aspects of the innate and adaptive immune system. Neutrophils are central to the pathogenesis of AAV as they are both the target of the autoantibody and effector cells mediating vascular injury. We describe mechanisms for ANCA induced activation of neutrophils, the pathogenic mechanisms by which this leads to endothelial cell injury, and how neutrophil crosstalk modulates other aspects of the immune system in AAV.