CD59

CD59, also known as protectin, is a small glycoprotein anchored to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. It is a member of the regulators of complement activation family and acts as a terminal regulator of the complement system.

Functionally, CD59 inhibits the formation of the membrane attack complex (MAC, C5b-9) by binding to C8 and C9 and preventing their polymerization, thereby protecting host cell membranes from lysis. As a GPI-anchored protein, its surface expression depends on intact GPI biosynthesis.

CD59 is broadly expressed on many cell types, with particularly high levels on erythrocytes, leukocytes, and platelets. Its expression can be reduced in conditions that disrupt GPI anchor formation, leading to increased susceptibility to complement-mediated damage.

Clinical relevance is most prominently illustrated by paroxysmal nocturnal hemoglobinuria (PNH). PNH results from somatic mutations in the PIGA gene in hematopoietic stem cells, causing loss of GPI anchors and absence of CD55 and CD59 on red cells. This renders red cells vulnerable to MAC-mediated lysis, contributing to intravascular hemolysis and a risk of thrombosis. CD59 deficiency can be diagnosed by flow cytometry assessing CD55 and CD59 on blood cells.

Therapeutically, inhibition of the terminal complement pathway with drugs such as eculizumab or ravulizumab reduces MAC formation and hemolysis in PNH and related disorders. Because terminal complement inhibition raises susceptibility to invasive meningococcal infection, vaccination is recommended for patients receiving these therapies.