Publication

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

van Timmeren, M. M. & Heeringa, P., Jan-2012, In : CURRENT OPINION IN RHEUMATOLOGY. 24, 1, p. 8-14 7 p.

Research output: Contribution to journalReview articleAcademicpeer-review

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
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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