New developments in the pathogenesis of ANCA-associated vasculitis

Abstract

In recent years there have been substantial developments in the understanding of the pathogenesis of ANCA-associated vasculitidies. Animal models have now been developed that finally prove a direct pathogenic role for ANCA, a subject fiercely debated since their original identification. We are also closer to understanding how ANCA exert their effects to cause disease. Progress has been made in elucidating how ANCA activate neutrophils, from how they bind antigen and where that antigen is located, to how antigen binding is translated into intracellular activity. The effects of ANCA activation on the effector functions of neutrophils and monocytes are being further dissected and the flow-based assay is allowing interactions with endothelium to be studied in more detail. Knowledge of the role of T cells has been enhanced by examining contributions to disease by differing subsets and their cytokine secretions. Defects in apoptosis playing a role in the initiation of other autoimmune diseases has prompted investigations into whether a similar pathogenesis is relevant in vasculitis, and various genetic polymorphisms have been discovered to be important in determining in whom vasculitis develops. This article reviews how recent research has helped in the understanding of the pathogenesis of small vessel vasculitis.