High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension.
Proc Natl Acad Sci U S A
; 116(50): 25236-25242, 2019 12 10.
Article
em En
| MEDLINE
| ID: mdl-31767751
ABSTRACT
Sickle cell disease (SCD) is caused by a variant hemoglobin molecule that polymerizes inside red blood cells (RBCs) in reduced oxygen tension. Treatment development has been slow for this typically severe disease, but there is current optimism for curative gene transfer strategies to induce expression of fetal hemoglobin or other nonsickling hemoglobin isoforms. All SCD morbidity and mortality arise directly or indirectly from polymer formation in individual RBCs. Identifying patients at highest risk of complications and treatment candidates with the greatest curative potential therefore requires determining the amount of polymer in individual RBCs under controlled oxygen. Here, we report a semiquantitative measurement of hemoglobin polymer in single RBCs as a function of oxygen. The method takes advantage of the reduced oxygen affinity of hemoglobin polymer to infer polymer content for thousands of RBCs from their overall oxygen saturation. The method enables approaches for SCD treatment development and precision medicine.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
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Hemoglobina Falciforme
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Hemoglobinas
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Eritrócitos
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Ensaios de Triagem em Larga Escala
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Anemia Falciforme
Tipo de estudo:
Evaluation_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article