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

Mirjan M. van Timmeren, Peter Heeringa*

*Bijbehorende auteur voor dit werk

Onderzoeksoutput: Review articlepeer review

33 Citaten (Scopus)


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.


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.

Originele taal-2English
Pagina's (van-tot)8-14
Aantal pagina's7
Nummer van het tijdschrift1
StatusPublished - jan-2012

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