TY - JOUR AU - David C. Rees, AU - Swee Lay Thein, AU - Anna Osei, AU - Emma Drasar, AU - Sanjay Tewari, AU - Anke Hannemann, AU - John S Gibson, PY - 2015/05/05 Y2 - 2024/03/28 TI - The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease JF - Haematologica JA - haematol VL - 100 IS - 5 SE - Articles DO - 10.3324/haematol.2014.120402 UR - https://haematologica.org/article/view/7367 SP - 595-600 AB - HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport100) and deoxygenated (K-Cl cotransport0) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport100: mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport0: mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit. ER -