title: Pathogenesis of ANCA-associated vasculitis:  recent insights from animal models.
abstract: OBJECTIVE
  To provide an update on animal models of antineutrophil cytoplasmic autoantibody (ANCA)-mediated vasculitis and highlight recent insights gained from studies in these models pertaining to immunopathogenesis.
  
  
  RESULTS
  Animal models support the pathogenic potential of myeloperoxidase (MPO)-ANCA. Alternative pathway complement activation has been identified as a novel inflammatory pathway in disease induction and a potential target for intervention. Interventions targeting B cells, antibodies, and signal transduction pathways may hold promise as well. The role of T cells is beginning to be explored, and studies indicate a prominent role for Th17 responses. The link between infection and ANCA vasculitis is well established. In animal models, Toll-like receptor (TLR)4 ligation is involved in disease induction. Ligation of TLRs contributes to the initiation of anti-MPO autoimmune responses in which TLR2 activation induces a Th17 response and TLR9 activation directs a Th1 response. An animal model for PR3-ANCA vasculitis is not available yet but models with a humanized immune system are being developed and show promising first results.
  
  
  CONCLUSIONS
  Animal models of MPO-ANCA vasculitis have contributed substantially to our understanding of disease immunopathogenesis and have illuminated novel targets for intervention. The development of PR3-ANCA animal models remains a challenge but recent observations in humanized model systems offer hope.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Mirjan M
authors.initials: MM
authors.lastname: van Timmeren
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
mesh_terms: D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000276:immunology; D051381:Rats; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D009195:Peroxidase