Erythrocyte Phosphorylation in Sickle Cell Disease

Sickle cell disease (SCD) is a hereditary disease that affects the red blood cells. This disease is seen throughout the world with a highest prevalence in Africa. It is caused by a simple mutation in the hemoglobin gene resulting in improper hemoglobin polymerization. This hemoglobinopathy is characterized by sickle shaped cells often combined several painful vaso-occlusion crises and anemia. Due to the chronic anemia, these patients often receive regular blood transfusions. In addition, SCD patients are often prescribed pain killers and given hydroxyurea to try and prevent/slow polymerization of the hemoglobin. Hydroxyurea is the only FDA approved drug for SCD even though the disease was discovered decades ago. SCD lacks treatment options due to the unknown causes of many of the physiological symptoms associated with the disease. The data within suggests a new target for SCD therapies, spleen tyrosine kinase (SYK). SYK is a kinase found in red cells that is important for many cellular functions. Inhibition of SYK would prevent hyperphosphorylation of band 3 (B3), membrane weakening, and vesiculation. Vesiculation causes the loss of membrane and the cells become denser, preventing them from being able to stretch and squeeze through small venules as they delivery oxygen to the tissues. Consequently, the red cells become stuck in the small venules and the MPs activate the immune system resulting in thrombosis and sticky leukocytes contributing to the occlusion of venules