Review: complement receptor 1 therapeutics for prevention of immune hemolysis

The complement system plays a crucial role in fighting infections and is an important link between the innate and adaptive immune responses. However, inappropriate complement activation can cause tissue damage, and it underlies the pathology of many diseases. In the transfusion medicine setting, complement sensitization of RBCs can lead to both intravascular and extravascular destruction. Moreover, complement deficiencies are associated with autoimmune disorders, including autoimmune hemolytic anemia (AIHA). Complement receptor 1 (CR1) is a large single-pass glycoprotein that is expressed on a variety of cell types in blood, including RBCs and immune cells. Among its multiple functions is its ability to inhibit complement activation. Furthermore, gene knockout studies in mice implicate a role for CR1 (along with the alternatively spliced gene product CR2) in prevention of autoimmunity. This review discusses the possibility that the CR1 protein may be manipulated to prevent and treat AIHA. In addition, it will be shown in an in vivo mouse model of transfusion reaction that recombinant soluble forms of CR1 can reduce complement-mediated RBC destruction, thereby prolonging survival of transfused RBCs. It is proposed that CR1-based therapeutics have potential for effective and safe prophylactic short-term use and for treatment of hemolytic transfusion reactions.