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.
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References
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
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
Jennette JC, Falk RJ (1997) Small-vessel vasculitis. N Engl J Med 337:1512–1523
Eisenberger U, Fakhouri F, Vanhille P et al (2005) ANCA-negative pauci-immune renal vasculitis: histology and outcome. Nephrol Dial Transplant 20:1392–1399
Lepse N, Abudalahad WH, Kallenberg CG et al (2011) Immune regulatory mechanisms in ANCA-associated vasculitides. Autoimmun Rev 11:77–83
Nauseef WM (2007) How human neutrophils kill and degrade microbes: an integrated view. Immunol Rev 219:88–102
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
Kallenberg CG (2011) Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: where to go? Clin Exp Immunol 164(Suppl. 1):1–3
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
Gan PY, Ooi JD, Kitching AR et al (2015) Mouse models of anti-neutrophil cytoplasmic antibody-associated vasculitis. Curr Pharm Des 21:2380–2390
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
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
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
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
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
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
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
Primo VC, Marusic S, Farnklin CC et al (2010) Anti-PR3 immune responses induce segmental and necrotizing glomerolonephritis. Clin Exp Immunol 159:327–337
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
Woodfin A, Voisin MB, Nourshargh S (2010) Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol 17:9–17
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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
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DOI: https://doi.org/10.1007/978-3-319-40136-2_2
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