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Pathogenesis of ANCA-associated vasculitis: recent insights from animal models

van Timmeren, Mirjan M.; Heeringa, Peter

Current Opinion in Rheumatology: January 2012 - Volume 24 - Issue 1 - p 8–14
doi: 10.1097/BOR.0b013e32834bde57
VASCULITIS SYNDROMES: Edited by Jochen Zwerina

Purpose of review 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.

Recent findings 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.

Summary 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.

Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands

Correspondence to P. Heeringa, Department of Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, EA11, 9713 GZ, Groningen, The Netherlands. Tel: +31 50 3610789; fax: +31 50 361 9911; e-mail:

© 2012 Lippincott Williams & Wilkins, Inc.