CD59: A long-known complement inhibitor has advanced to a blood group system

Area of Science:

• Immunology
• Hematology
• Genetics

Background:

• CD59 is a membrane glycoprotein protecting cells from complement-mediated damage by inhibiting the membrane attack complex (MAC).
• Defects in the glycosylphosphatidylinositol (GPI) anchor of CD59 result in its absence from cell membranes, increasing susceptibility to complement.
• Paroxysmal nocturnal hemoglobinuria (PNH) involves red blood cell clones with defective GPI-anchored proteins, including CD59, leading to hemolysis and thrombosis.

Purpose of the Study:

• To introduce CD59 as a newly recognized blood group system (number 35).
• To discuss the clinical implications of CD59 deficiency and the recent discovery of CD59 alloantibodies.

Main Methods:

• Review of existing literature on CD59 function, genetics, and clinical manifestations.
• Classification of CD59 as a blood group system by the International Society of Blood Transfusion.

Main Results:

• CD59 is essential for protecting cells, particularly erythrocytes, from complement attack.
• CD59 deficiency, often linked to GPI anchor defects, causes severe clinical symptoms like neuropathy, strokes, and hemolysis.
• The first CD59-specific alloantibody was identified in a CD59-deficient child.

Conclusions:

• CD59 represents a significant blood group system with critical implications for transfusion medicine and understanding complement-related disorders.
• CD59 deficiency presents with severe, often fatal, clinical manifestations, emphasizing the need for further research and potential therapeutic strategies.
• The complement inhibitor eculizumab has shown promise in improving clinical outcomes for individuals with CD59 deficiency.