Regulation of complement activation on red blood cells

The complement system is a crucial part of our innate immune system and is important as first line of defense against pathogens. Next to pathogen clearance, the complement system also plays an important role in removing damaged or dying cells from the body. Red bloods cells (RBCs) are the most common type of blood cells and while circulating in the body being continuously in contact with complement components dissolved in the blood plasma. To protect against unwanted complement activation, RBCs (like all host cells) are equipped with several complement regulating proteins, either expressed on the cell membrane such as CD35, CD55 and CD59 or acting in the fluid phase such as factor H (FH). Inefficient regulation or overstimulation of the complement system may cause complement deposition on RBCs. This can result into intravascular and/or extravascular clearance of RBCs both contributing to the development of anemia such as in autoimmune hemolytic anemia (AIHA) and paroxysmal nocturnal hemoglobinuria (PNH). RBC transfusions are given to restore oxygen transporting capacity when there are clear signals of lack of oxygen due to anemia. The aim of this thesis is to further elucidate how complement activation is regulated on RBCs, under normal conditions, during RBC transfusion and in hemolytic diseases.