High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension
High-throughput assessment of hemoglobin polymer in single red blood cells from sickle cell patients under controlled oxygen tension
复制标题
DOI：
10.1073/pnas.1914056116
复制
发表时间：
2019-12-10
影响因子：
11.1
通讯作者：
Higgins, John M.
中科院分区：
文献类型：
--
作者：
Di Caprio, Giuseppe;Schonbrun, Ethan;Higgins, John M.
镰状细胞病（SCD）是由一种变异的血红蛋白分子引起的，该分子在氧张力降低的情况下在红细胞（rbc）内聚合。这种典型的严重疾病的治疗进展缓慢，但目前对诱导胎儿血红蛋白或其他非镰状血红蛋白亚型表达的治疗性基因转移策略持乐观态度。所有SCD的发病率和死亡率都直接或间接地由单个红细胞的聚合物形成引起。因此，确定并发症风险最高的患者和具有最大治愈潜力的候选治疗方案需要在控制氧的情况下确定个体红细胞中的聚合物含量。在这里，我们报告了血红蛋白聚合物在单个红细胞中的半定量测量作为氧的功能。该方法利用血红蛋白聚合物的氧亲和力降低，从红细胞的总体氧饱和度推断出数千个红细胞的聚合物含量。该方法为SCD治疗发展和精准医学提供了途径。
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 semi-quantitative 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.