The
blood group system number 35 is based on CD59, a 20-kDa
membrane glycoprotein present on a large number of different cells, including erythrocytes. The major function of CD59 is to protect cells from
complement attack. CD59 binds to
complement components CS and C9 and prevents the polymerization of C9, which is required for the formation of the
membrane attack complex (MAC). Other functions of CD59 in cellular immunity are less well defined. CD59 is inserted into the membrane by a
glycosylphosphatidylinositol (GPI) anchor. A defect of this anchor causes lack of this
protein from the cell membrane, which leads to an enhanced sensitivity towards
complement attack. Patients with
paroxysmal nocturnal hemoglobinuria (PNH) harbor a varying percentage of red blood cell clones with a defect in
GPI-anchored proteins, including CD59. The most characteristic symptoms of this disease are episodes of
hemolysis and
thromboses. Although CD59 has been classified as a
membrane protein for more than 25 years, an alloantibody directed against CD59 was found only recently. So far, the first and sole alloantibody described was detected in a CD59-deficient child. In 2014, CD59 received the status of a
blood group system by the International Society for
Blood Transfusion Red Cell Immunogenetics and
Blood Group Terminology Working Party. Among a variety of almost 20 synonyms, the designation CD59 was chosen for the
blood group system and CD59.l for the wild-type
protein. The only three alleles published to date are null alleles. All CD59-deficient individuals recognized so far were severely ill, two of whom have died. Most of the reported cases present with a typical clinical picture within the first year of life that includes neuropathy,
strokes, and mild Coombs-negative
hemolysis. In one published case, the application of the
complement inhibitor eculizumab caused a pronounced improvement of the clinical situation.