Disease mechanism

The interaction between the activated alternative complement pathway, neutrophils and C5a is at the heart of vasculitic damage in AAV.1

AAV pathogenesis

The development of AAV is a complex and multifactorial autoimmune process2,3

The initial causes of AAV are currently unclear.2,3 Predisposing factors such as microbial infection, genetic influence, environmental agents and specific drugs are all fundamental to the development of AAV.2,3

Exposure to silica, pesticides, fumes, construction materials, hydrocarbon (cleaning agents, paint, diesel), drugs (propylthiouracil, hydralazine, D-penicillamine, cefotaxime, minocycline, anti-TNF agents, phenytoin) and certain psychoactive agents may all cause AAV.2,3

References & footnotes
  • Stage 1
  • Stage 2

ANCA involvement
Loss of immune tolerance to ANCA antigens and development of ANCA by plasma cells1

ANCA are most commonly directed against the neutrophil lysosomal enzymes PR3 and MPO in GPA (Granulomatosis with Polyangiitis, previously called Wegener’s) and MPA (Microscopic Polyangiitis), respectively1-5

References & footnotes


The importance of complement and neutrophils in AAV activation

C5a plays a major role in the pathogenesis of AAV, amplifying ANCA-induced inflammation and vascular damage1

vasculitis pathways diagram schema
vasculitis pathways diagram schema mobile                

References & footnotes