Page 109 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

In: The Vasculitides, Volume 1 ISBN: 978-1-63463-110-5
Editors: David S. Younger © 2015 Nova Science Publishers, Inc.

Chapter 4

Experimental Autoimmune Vasculitis:
Insights into Human Vasculitis
Using Animal Models

Alan D. Salama, M.B., B.S., M.A., Ph.D.?
and Mark A. Little, F.R.C.P., Ph.D.

UCL Centre for Nephrology, London and Trinity Health
Kidney Centre, Trinity College, Dublin, Ireland

Abstract

Over the last decade several different experimental models have been described that
try to recapitulate the clinical features of ANCA associated vasculitis. Although all are
limited to some extent in their ability to mirror human disease, together they have
provided important and sometimes unexpected insights into disease pathogenesis, as well
as new avenues for therapeutic innovation.

Rodent models of both MPO-, and more recently, PR3-ANCA associated vasculitis
have replicated some of the clinical features found in affected patients with ANCA-
associated vasculitis (AAV), notably with pulmonary and renal involvement. The vast
majority of successful work in this field has concerned MPO-AAV, yet there remains the
need for a better model for aspects of PR3-AAV, including the granulomatous lesions
found in granulomatosis with polyangiitis, and the relapsing nature of the illness. By
virtue of the means by which they are induced and their time course, such experimental
animal models have not replicated the complex and varied human disease AAV
phenotype. However, the effector pathways and the final organ damage appear very
similar to those found clinically, allowing many conclusions to be drawn regarding
disease etiology. This chapter reviews the salient experimental animal models that
replicate the vasculitic lesions in human AAV. Further refinement of these models may
yield the full spectrum of the human condition, providing insight regarding organ tropism
and therapeutic targets for disease subtypes.

? Corresponding author: Alan Salama. UCL Centre for Nephrology Royal Free Hospital, Rowland Hill Street,
London NW3 2PF, UK. E-mail: [email protected].

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