Abstract
INTRODUCTION: Complement was long thought not to be involved in ANCA vasculitis pathogenesis until studies in murine models demonstrated its central role. The current theory is ANCA-activated neutrophils degranulate and release factors that activate complement, which, in turn, recruits more neutrophils and causes an inflammatory amplification loop that results in the vascular inflammation characteristic of disease. Targeting this amplification loop through complement inhibition has proven to be effective in ANCA vasculitis treatment. AREAS COVERED: A PubMed search was conducted using key terms 'ANCA vasculitis' AND 'complement system.' We review the findings from experimental mouse models, in vitro studies, and human ANCA vasculitis that support a role for complement activation in disease pathogenesis. We also summarize results from pivotal clinical studies demonstrating the safety and efficacy of complement inhibition in ANCA vasculitis treatment. EXPERT OPINION: While complement activation is undoubtedly involved in ANCA vasculitis pathogenesis, less clear is whether measuring complement activation markers can reliably assess disease activity, predict those who will benefit from complement-targeting therapy, or identify patients in stable remission and able to stop therapy. Better understanding the clinical implications of complement activation will shed more light on the utility of complement inhibition and facilitate precision medicine in ANCA vasculitis.