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

Mirjan M. van Timmeren, Peter Heeringa*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8-14
Number of pages7
JournalCURRENT OPINION IN RHEUMATOLOGY
Volume24
Issue number1
DOIs
Publication statusPublished - Jan-2012

Keywords

  • animal models
  • antineutrophil cytoplasmic autoantibodies
  • vasculitis
  • ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES
  • IGG GLYCAN HYDROLYSIS
  • INTERACTIONS IN-VIVO
  • WEGENERS-GRANULOMATOSIS
  • ANTIMYELOPEROXIDASE ANTIBODIES
  • MEDIATED GLOMERULONEPHRITIS
  • HUMAN NEUTROPHILS
  • TH17 CELLS
  • AUTOANTIBODIES
  • MICE

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