High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension

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Caprio, Giuseppe Di and Schonbrun, Ethan and Gonçalves, Bronner P. and Valdez, Jose M. and Wood, David K. and Higgins, John M. (2019) High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension. Proceedings of the National Academy of Sciences of the United States of America, 116 (50). pp. 25236-25242. 31767751. ISSN 0027-8424 (https://doi.org/10.1073/pnas.1914056116)

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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.

ORCID iDs

Caprio, Giuseppe Di ORCID logoORCID: https://orcid.org/0000-0001-5564-8064, Schonbrun, Ethan, Gonçalves, Bronner P., Valdez, Jose M., Wood, David K. and Higgins, John M.;
  • Item type:Article
    ID code:85650
    Dates:
    Date
    Event
    10 December 2019
    Published
    25 November 2019
    Published Online
    30 October 2019
    Accepted
    13 August 2019
    Submitted
    Notes:Funding Information: ACKNOWLEDGMENTS. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network under Award ECCS-1542202. This work was supported by National Heart, Lung, and Blood Institute Grants HL130818 and HL132906. We thank Chhaya Patel and Hasmukh Patel for assistance with blood sample collection, Carlo Brugnara and Frank Bunn for helpful discussions, and the editor and 2 anonymous reviewers for helpful comments and suggestions. Publisher Copyright: © 2019 National Academy of Sciences. All rights reserved.
    Subjects:Medicine
    Department:Faculty of Engineering > Biomedical Engineering
    Depositing user: Pure Administrator
    Date deposited:01 Jun 2023 09:52
    Last modified:18 Dec 2024 01:36
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/85650
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