The rise of complement in ANCA-associated vasculitis: from marginal player to target of modern therapy.

The rise of complement in ANCA-associated vasculitis: from marginal player to target of modern therapy. Clin Exp Immunol. 2020 Sep 18;: Authors: Trivioli G, Vaglio A Abstract The complement system plays a central role in autoimmune diseases, including ANCA-associated vasculitis (AAV). Although complement deposition is scarce in AAV pathological samples, complement activation is required for development of necrotizing crescentic glomerulonephritis (NCGN) in mouse models of AAV and occurs via the alternative pathway. The anaphylatoxin C5a, produced by the final complement pathway, is determinant to drive the disease in animal models. C5a primes human neutrophils and enhances their activation induced by ANCA; activated neutrophils in turn release factors that lead to C5a generation, establishing a self-amplifying loop. C5a is also significantly increased in the serum of AAV patients with active disease compared to those in remission or healthy controls. Inhibition of the C5a receptor with avacopan is an emerging therapy that will likely allow AAV treatment with glucocorticoid-free regimens. PMID: 32946609 [PubMed - as supplied by publisher]
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research