Title:Mouse Models of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Volume: 21
Issue: 18
Author(s): Poh-Yi Gan, Joshua D. Ooi, A. Richard Kitching and Stephen R. Holdsworth
Affiliation:
Keywords:
ANCA, vasculitis, myeloperoxidase, proteinase-3, MPA, GPA, animal models.
Abstract: Inflammation of blood vessels (vasculitis) results from many pathological processes and is found in
many different diseases. However, in most situations, the pathological processes inducing vasculitis are unknown.
The discovery of anti-neutrophil cytoplasmic autoantibodies (ANCAs) in the 1980s opened the door for studies that
eventually led to the description of a new previously undescribed disease, ANCA-associated vasculitis (AAV). Unravelling
the immunopathogenesis of this new disease resulted largely from the development of animal models.
The major breakthroughs were the description of ANCA, its association with small vessel vasculitis and the discovery
of its target autoantigens (myeloperoxidase and Proteinase 3). Three major disease syndromes comprise the
AAVs, microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis
(EGPA). Recent human studies suggest that proteinase 3 and myeloperoxidase associated vasculitis are two
separate but related diseases. The ability to induce murine autoimmunity to myeloperoxidase including ANCA (with the same immune
staining patterns as human ANCA) and the capacity of this anti-myeloperoxidase autoimmunity to induce disease with many of the characteristic
features of human AAV are well developed. However, the development of animal models of anti-proteinase 3 ANCA and
EGPA is much less well developed. Animal models are important in understanding the human disease and in particular in defining potential
therapeutic targets and in early stage therapeutic testing of potential drugs. Clearly the relevance of animal models depends on how
closely they mimic human diseases. The current status of animal models of vasculitis will be described in detail with reference to these
criteria.
