ANCA-associated vasculitis and the mechanisms of tissue injury


  • A. Schreiber
  • M. Choi


  • 141-158


  • ANCA associated vasculitides (AAVs) comprise four different disease entities: I) granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis), II) microscopic polyangiitis (MPA), III) eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome), and IV) renal-limited vasculitis or isolated pauci-immune necrotizing and crescentic glomerulonephritis (NCGN). Experimental data support the notion that ANCA-induced activation of both neutrophils and monocytes is one of the main pathogenic mechanisms involved in disease induction. Binding of ANCA IgG to surface expressed ANCA antigens on myeloid cells leads to generation of reactive oxygen species (ROS), degranulation and activation of proteases, and formation of neutrophil extracellular traps (NET). Finally, activation of the complement system in AAVs by ANCA stimulated neutrophils leads to generation of C5a, which plays an important role in an amplifying inflammatory loop.