Complement in ANCA-associated vasculitis: mechanisms and implications for management.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. The main histological feature in the kidneys of patients with AAV is pauci-immune necrotizing crescentic glomerulonephritis with little immunoglobulin and complement deposition in the glomerular capillary walls. The complement system was not, therefore, initially thought to be associated with the development of AAV. Accumulating evidence from animal models and clinical observations indicate, however, that activation of the complement system - and the alternative pathway in particular - is crucial for the development of AAV, and that the complement activation product C5a has a central role. Stimulation of neutrophils with C5a and ANCA not only results in the neutrophil respiratory burst and degranulation, but also activates the coagulation system and generates thrombin, thus bridging the inflammation and coagulation systems. In this Review, we provide an overview of the clinical, in vivo and in vitro evidence for a role of complement activation in the development of AAV and discuss how targeting the complement system could provide opportunities for therapy.
Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P. R. China.
Min
M
Chen
Department of Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, Cambridge, UK.
David R W
DRW
Jayne
Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, P. R. China.
Ming-Hui
MH
Zhao
D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy / Q000276:immunology*; D003167:Complement Activation; D003165:Complement System Proteins; D006801:Humans
D003165:Complement System Proteins