DAF

DAF (CD55) normally binds to C3b and C4b, destabilizing the C3 and C5 convertases of both the classical and alternative complement pathways, thereby preventing excessive complement activation on self-cells. It is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor, similar to CD59 (membrane inhibitor of reactive lysis), which blocks the membrane attack complex (MAC) formation. In paroxysmal nocturnal hemoglobinuria (PNH), an acquired mutation in the PIGA gene (on the X chromosome) in hematopoietic stem cells leads to defective synthesis of GPI anchors. This results in loss of both DAF and CD59 from the surface of blood cells, rendering red blood cells, platelets, and white blood cells susceptible to unchecked complement-mediated destruction. Clinically, PNH presents with intravascular hemolysis (hemoglobinuria, especially morning urine), thrombosis (notably in hepatic, portal, or cerebral veins), and pancytopenia due to bone marrow failure. Diagnosis is confirmed via flow cytometry showing deficient CD55/CD59 expression on blood cells (often using the FLAER test). Treatment includes eculizumab or ravulizumab, monoclonal antibodies that inhibit terminal complement component C5, preventing MAC formation and hemolysis. DAF also plays roles in other immune regulatory contexts, including as a receptor for certain pathogens (e.g., some strains of E. coli and enteroviruses use DAF for cell entry).