Skip to main content

Animal Models of ANCA-Associated Vasculitides

  • Chapter
  • First Online:
Systemic Vasculitides: Current Status and Perspectives

Abstract

Antibodies against neutrophil proteins myeloperoxidase (MPO) and proteinase-3 (PR3) are responsible for the development of anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAV). Although the knowledge of these conditions is remarkably improved in the last few years, their etiology and pathogenetic mechanism(s) are still poorly understood. The establishment of experimental models has been repeatedly attempted with the aim of achieving a deeper understanding of their human counterpart. Here, we discuss the principal animal models currently used to investigate the mechanisms underlying the onset of AAV.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mantovani A, Cassatella MA, Costantini C et al (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531

    Article  CAS  PubMed  Google Scholar 

  2. van der Woude FJ, Rasmussen N, Lobatto S et al (1985) The TH. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener’s granulomatosis. Lancet 1:425–429

    Article  PubMed  Google Scholar 

  3. Jennette JC, Falk RJ (1997) Small-vessel vasculitis. N Engl J Med 337:1512–1523

    Article  CAS  PubMed  Google Scholar 

  4. Eisenberger U, Fakhouri F, Vanhille P et al (2005) ANCA-negative pauci-immune renal vasculitis: histology and outcome. Nephrol Dial Transplant 20:1392–1399

    Article  PubMed  Google Scholar 

  5. Lepse N, Abudalahad WH, Kallenberg CG et al (2011) Immune regulatory mechanisms in ANCA-associated vasculitides. Autoimmun Rev 11:77–83

    Article  CAS  PubMed  Google Scholar 

  6. Nauseef WM (2007) How human neutrophils kill and degrade microbes: an integrated view. Immunol Rev 219:88–102

    Article  CAS  PubMed  Google Scholar 

  7. Hajjar E, Broemstrup T, Kantari C et al (2010) Structures of human proteinase 3 and neutrophil elastase so similar yet so different. FEBS J 277:2238–2254

    Article  CAS  PubMed  Google Scholar 

  8. Kallenberg CG (2011) Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: where to go? Clin Exp Immunol 164(Suppl. 1):1–3

    Article  Google Scholar 

  9. Gregersen JW, Kristensen T, Krag SR et al (2012) Early plasma exchange improves outcome in PR3-ANCA-positive renal vasculitis. Clin Exp Rheumatol 30:S39–S47

    PubMed  Google Scholar 

  10. Gan PY, Ooi JD, Kitching AR et al (2015) Mouse models of anti-neutrophil cytoplasmic antibody-associated vasculitis. Curr Pharm Des 21:2380–2390

    Article  CAS  PubMed  Google Scholar 

  11. Xiao H, Heeringa P, Liu Z et al (2002) Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 110:955–963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xiao H, Heeringa P, Liu Z et al (2005) The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies. Am J Pathol 167:39–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schreiber A, Xiao H, Falk RJ et al (2006) Bone marrow-derived cells are sufficient and necessary targets to mediate glomerulonephritis and vasculitis induced by anti-myeloperoxidase antibodies. J Am Soc Nephrol 17:3355–3364

    Article  PubMed  Google Scholar 

  14. Jennette JC, Xiao H, Falk R et al (2011) Experimental models of vasculitis and glomerulonephritis induced by antineutrophil cytoplasmic autoantibodies. Contrib Nephrol 169:211–220

    Article  CAS  PubMed  Google Scholar 

  15. Ruth AJ, Kitching AR, Kwan RYQ et al (2006) Anti-neutrophil cytoplasmic antibodies and effector CD4+ cells play nonreduntant roles in anti-myeloperoxidase crescentic glomerulonephritis. J Am Soc Nephrol 17:1940–1949

    Article  CAS  PubMed  Google Scholar 

  16. Huugen D, Xiao H, van Esch A et al (2005) Aggravation of anti-myeloperoxidase antibody-induced glomerulonephritis by bacterial lipopolysaccharide: role of tumor necrosis factor-alpha. Am J Pathol 167:47–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Little MA, Bhangal G, Smyth CL et al (2006) Therapeutic effect of anti-TNF-alpha antibodies in an experimental model of anti-neutrophil cytoplasm antibody-associated systemic vasculitis. J Am Soc Nephrol 17:160–169

    Article  CAS  PubMed  Google Scholar 

  18. Primo VC, Marusic S, Farnklin CC et al (2010) Anti-PR3 immune responses induce segmental and necrotizing glomerolonephritis. Clin Exp Immunol 159:327–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Little MA, Al-Ani B, Ren S et al (2012) Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PLoS One 7, e28626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Woodfin A, Voisin MB, Nourshargh S (2010) Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol 17:9–17

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Domenico Ribatti .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Ribatti, D., Dammacco, F. (2016). Animal Models of ANCA-Associated Vasculitides. In: Dammacco, F., Ribatti, D., Vacca, A. (eds) Systemic Vasculitides: Current Status and Perspectives. Springer, Cham. https://doi.org/10.1007/978-3-319-40136-2_2

Download citation

Publish with us

Policies and ethics