Complement: A primer for the coming therapeutic revolution

Abstract

The complement system is an important part of the innate and adaptive immune systems. Originally characterized as a single serum component contributing to the killing of bacteria, we now know that there are close to sixty complement proteins, multiple activation pathways and a wide range of effector functions mediated by complement. The system plays a critical role in host defense against bacteria, viruses, fungi and other pathogens. However, inappropriate complement activation contributes to the pathophysiology of autoimmune diseases and many inflammatory syndromes. Over the last several decades, therapeutic approaches to inhibit complement activation at various steps in the pathways have met with initial success, particularly at the level of the terminal pathway. This success, combined with insight from animal model studies, has lead to an unprecedented effort by biotech and pharmaceutical companies to begin developing complement inhibitors. As a result, complement has been brought for the first time to the attention of pharmacologists, toxicologists, project managers and others in the drug development industry, as well as those in the investment world. The purpose of this primer is to provide a broad overview of complement immunobiology to help those new to complement understand the rationale behind the current therapeutic directions and the investment potential of these new therapeutics.

Keywords: Complement; Host defense; Inflammation; Innate immunity.