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The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.


Type

Article

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Authors

Rees, David C 
Thein, Swee Lay 
Osei, Anna 
Drasar, Emma 
Tewari, Sanjay 

Abstract

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 cotransport(100)) and deoxygenated (K-Cl cotransport(0)) 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 cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): 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.

Description

Keywords

Adolescent, Adult, Anemia, Sickle Cell, Child, Child, Preschool, Erythrocytes, Erythrocytes, Abnormal, Female, Hemoglobin SC Disease, Hospitalization, Humans, Male, Symporters, Young Adult, K Cl- Cotransporters

Journal Title

Haematologica

Conference Name

Journal ISSN

0390-6078
1592-8721

Volume Title

100

Publisher

Ferrata Storti Foundation (Haematologica)
Sponsorship
Medical Research Council (G0901177)
This study was funded by the Medical Research Council, UK Project Grant (92150).