Pathogenic role of anti-neutrophil cytoplasmic antibodies in vasculitis.

The pathogenicity of anti-neutrophil cytoplasmic antibodies (ANCAs) in ANCA-associated vasculitis has been debated for some time. Animal models have recently demonstrated that ANCAs are a transferable cause of disease and this is supported by studies of the effects of ANCAs on neutrophil-endothelial cell interactions under flow. ANCAs activate neutrophils by cross-linking target antigens on the neutrophil surface with Fc receptors, thereby recruiting signal transduction pathways that promote neutrophil adhesion, degranulation and respiratory burst. Activated neutrophils in proximity with endothelial cells are believed to initiate injury.