Animal models of antineutrophil cytoplasm antibody-associated vasculitis

Abstract

To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue. Rodent models of both myeloperoxidase (MPO) ANCA and proteinase 3 (PR3) ANCA associated vasculitis have been developed, which have provided important insights into the pathogenesis of ANCA-associated pulmonary and renal disease. The vast majority of in-vivo work in this field has concerned MPO-ANCA associated disease, although the last year has seen some advances in the modelling of anti-PR3 disease. As with all experimental animal models, they are flawed in one way or another by virtue of the means by which they are induced, but they have already provided novel directions for future intervention in these complex diseases. To date, there are no good models that replicate the granulomatous lesions found in granulomatosis with polyangiitis (GPA, formerly Wegener's) or the development of vasculitis lesions in organs other than the lungs or kidneys. ANCA-associated vasculitis can be induced in various forms in susceptible rodents. Further refinements are required for the full spectrum of disease phenotype to be replicated in animals, but critical new targets have been proposed based on the use of molecular blocking agents and transgenic animals to elucidate disease pathways.