Complement Biology
The complement system consists of approximately 20 proteins found in the blood. When stimulated by one of several triggers, the complement system becomes activated and enzymes in the system cleave specific complement proteins, leading to further activation of the cascade. When uncontrolled, this activation cascade can result in a massive inflammatory response, leading to substantial tissue and organ damage. Normally, complement activation is controlled by specific naturally occurring soluble and membrane-bound inhibitors of the complement cascade called complement regulatory proteins.
However, when complement activation is uncontrolled, it can lead to severe and life-threatening conditions. For example, in PNH and aHUS, specific genetic errors lead to a deficiency in complement regulatory proteins that normally protect healthy cells, resulting in uncontrolled complement activation and severe, life-threatening clinical consequences.1,2,3
Given the critical role of the complement system in a wide range of diseases, complement inhibition has broad implications for transforming treatment paradigms and improving patients’ lives.
References
- Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995. 9;333(19):1253-8.
- Noris M, Remuzzi G: Atypical hemolytic-uremic syndrome. N Engl J Med 2009 361:1676-87
- Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin Nephrol Hypertens 2010 May;19(3):242-7