Complement dysregulation and disease: from genes and proteins to diagnostics and drugs

Abstract

During the last decade, numerous studies have associated genetic variations in complement components and regulators with a number of chronic and infectious diseases. The functional characterization of these complement protein variants, in addition to recent structural advances in understanding of the assembly, activation and regulation of the AP C3 convertase, have provided important insights into the pathogenic mechanisms involved in some of these complement related disorders. This knowledge has identified potential targets for complement inhibitory therapies which are demonstrating efficacy and generating considerable expectation in changing the natural history of these diseases. Comprehensive understanding of the genetic and non-genetic risk factors contributing to these disorders will also result in targeting of the right patient groups in a stratified medicine approach through better diagnostics and individually tailored treatments, thereby improving management of patients.