Pathophysiology of ANCA-associated vasculitis.

Abstract

ANCA positive vasculitis (AAV) is a serious autoimmune disease mainly affecting small vessels in various organ systems, accompanied by the presence of ANCA antibodies in serum. AAV represents a group of the most common systemic vasculitis in adulthood, and based on clinical manifestations this disease entity includes 3 phenotypes, namely: granulomatosis with polyangiitis (formerly Wegeners granulomatosis), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). Similar to other autoimmune diseases, AAV develops in patients with a predisposing genetic background who have been exposed to causative environmental factors, such as infections. The mechanisms by which ANCA antibodies cause vasculitis involves excessive neutrophil activation, that subsequently leads to release pro-inflammatory cytokines, reactive oxygen species and lytic enzymes. In addition, activated neutrophils induce the formation of neutrophil extracellular traps in a process called NETosis. The released neutrophil antigens are exposed to the immune system via antigen presenting cells, which further stimulates antibody production and creates a vicious circle with tissue destruction. Understanding the pathogenesis of AAV represents the key which provides not only optimal diagnosis and treatment, but also gives the pathologist a tool for deeper insight into the morphological features of disease progression, including the various stages of development and healing.