Stem cell transplantation for paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rareblood disease that results from clonal expansion of amultipotent hematolopoietic stem cell harboring a PIG-A mutation.1 The PIG-A gene product is required for the biosynthesis of glycophosphatidylinositol anchors, a glycol-ipid moiety that tethers dozens of proteins to lipid bilayer of cell membranes. Consequently, the PNH stem cell and its progeny have a reduction or absence of all GPI-anchored pro-teins. Two of these proteins, CD55 and CD59, are comple-ment regulatory proteins and are fundamental to the patho-physiology of paroxysmal nocturnal hemoglobinuria.2,3 CD55 inhibits C3 convertases and CD59 blocks formation of the membrane attack complex (MAC). The loss of complement regulatory proteins renders PNH erythrocytes susceptible to both intravascular (due to CD59 deficiency) and extravascu-lar (due to CD55 deficiency) hemolysis, but it is the intravas-cular hemolysis that contributes to much of the morbidity