Many details of the complement cascade were worked out more than 60 years ago. The innate immune system offers protection from certain bacterial infections, but complement was not thought to play a major role in human disease. Over the past 2 decades it has become clear that the complement cascade plays a vital role in shaping adaptive immunity and that failure to regulate complement is a principal driver of many human diseases including cold agglutinin disease, paroxysmal nocturnal hemoglobinuria, thrombotic microangiopathies, HELLP syndrome and others. Importantly, there are now numerous drugs that target complement that have changed the natural history of many of these previously life-threatening conditions that are frequently encountered by hematologists. This Presidential Symposium will cover the canonical extracellular complement cascade, intracellular complement, and targeted complement inhibitor drugs that have changed the natural history of complement-driven diseases.

Dr. Lubka Roumenina will discuss canonical complement pathways, the importance of the innate immune system. She will also discuss diseases associated with failure to regulate complement on host cells and the role of complement in thromboinflammation.

Dr. Claudia Kemper will discuss the role of intracellular complement in training the adaptive immune system and potential role intracellular complement activation in human disease. Non-canonical functions of complement that participate in cell metabolism and autophagy will be discussed.

Dr. Eleni Gavriilaki will cover a variety of old and new complement inhibitors to treat complementopathies. She will discuss inhibitors that block at C5, C3, C1s and the alternative pathway. These inhibitors can be administered by intravenous infusion, subcutaneous injections and now oral. Advantages and disadvantages and efficacy of these complement inhibitors in a variety of human diseases will be discussed.