Complement in ANCA-associated vasculitis

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases with rapid progression and poor prognosis. The histopathological hallmark in the kidneys of patients with AAV is pauci-immune necrotizing crescentic glomerulonephritis, therefore complement was previously suggested not to play a major role in the disease development. However, in the recent years, accumulating evidence from both experimental and clinic study has strongly incriminated alternative complement pathway activation as critically important in the pathogenesis of AAV. In patients with AAV, plasma levels of Bb and FH, components of the alternative complement pathway, are associated with disease activity and prognosis, which might be useful biomarkers in monitoring systemic disease activity and renal disease activity in AAV. The complement activation product C5a and its interaction with C5a receptor play a central role. It is suggested that neutrophils, ANCA and complement system form a positive feedback loop contributing to the development of AAV. Preliminary data of two clinical trials have demonstrated effectiveness and safety of C5a receptor blockade in patients with AAV. Therefore, measurement of complement biomarkers will be helpful in assessing the disease activity of patients and be of great importance for monitoring the efficiency of complement-targeting therapy in the future.(Chin J Lab Med, 2017, 40: 672-676) Key words: Anti-neutrophil cytoplasmic antibody-associated vasculitis; Complement C5 convertase, alternative pathway; Receptor, anaphylatoxin C5a