Figure 2.

Targeting of the complement cascade in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. ANCA activation of primed neutrophils stimulates degranulation and release of reactive oxygen species (ROS), leading to tissue damage. In addition, ANCA activation leads to the production of factor B and properdin, which serve to activate the alternative complement pathway. Complement component 5a (C5a) enhances the inflammatory response by recruiting and priming additional neutrophils for ANCA activation. Disease activity can be controlled by targeting C5 (eculizumab), C5a (IFX-1), or the C5a receptor (C5aR; avacopan). Notably, targeting of C5 also prevents activation of the membrane attack complex (MAC). NETosis, cell death through release of neutrophil extracellular traps.