Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian Hospital, New York, New York, USA.
University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado, USA.
J Clin Invest. 2020 May 1;130(5):2270-2285. doi: 10.1172/JCI133530.
BACKGROUNDGlucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.METHODSMale volunteers were screened for G6PD deficiency; 27 control and 10 G6PD-deficient volunteers each donated 1 RBC unit. After 42 days of refrigerated storage, autologous 51-chromium 24-hour posttransfusion RBC recovery (PTR) studies were performed. Metabolomics analyses of these RBC units were also performed.RESULTSThe mean 24-hour PTR for G6PD-deficient subjects was 78.5% ± 8.4% (mean ± SD), which was significantly lower than that for G6PD-normal RBCs (85.3% ± 3.2%; P = 0.0009). None of the G6PD-normal volunteers (0/27) and 3 G6PD-deficient volunteers (3/10) had PTR results below 75%, a key FDA acceptability criterion for stored donor RBCs. As expected, fresh G6PD-deficient RBCs demonstrated defects in the oxidative phase of the pentose phosphate pathway. During refrigerated storage, G6PD-deficient RBCs demonstrated increased glycolysis, impaired glutathione homeostasis, and increased purine oxidation, as compared with G6PD-normal RBCs. In addition, there were significant correlations between PTR and specific metabolites in these pathways.CONCLUSIONBased on current FDA criteria, RBCs from G6PD-deficient donors would not meet the requirements for storage quality. Metabolomics assessment identified markers of PTR and G6PD deficiency (e.g., pyruvate/lactate ratios), along with potential compensatory pathways that could be leveraged to ameliorate the metabolic needs of G6PD-deficient RBCs.TRIAL REGISTRATIONClinicalTrials.gov NCT04081272.FUNDINGThe Harold Amos Medical Faculty Development Program, Robert Wood Johnson Foundation grant 71590, the National Blood Foundation, NIH grant UL1 TR000040, the Webb-Waring Early Career Award 2017 by the Boettcher Foundation, and National Heart, Lung, and Blood Institute grants R01HL14644 and R01HL148151.
背景
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症降低了红细胞（RBC）耐受氧化应激的能力。冷藏储存 RBC 会诱导氧化应激。我们假设与 G6PD 正常 RBC 相比，G6PD 缺乏供体 RBC 的输血储存质量较差。
方法
筛选男性志愿者 G6PD 缺乏症；27 名对照志愿者和 10 名 G6PD 缺乏志愿者每人捐献 1 单位 RBC。冷藏储存 42 天后，进行自体 51 铬 24 小时输注后 RBC 回收率（PTR）研究。还对这些 RBC 单位进行了代谢组学分析。
结果
G6PD 缺乏组的平均 24 小时 PTR 为 78.5%±8.4%（平均值±标准差），明显低于 G6PD 正常 RBC 的 85.3%±3.2%（P=0.0009）。没有一名 G6PD 正常志愿者（0/27）和 3 名 G6PD 缺乏志愿者（3/10）的 PTR 结果低于 75%，这是 FDA 接受储存供体 RBC 的关键标准。正如预期的那样，新鲜的 G6PD 缺乏 RBC 显示戊糖磷酸途径氧化阶段的缺陷。在冷藏储存过程中，与 G6PD 正常 RBC 相比，G6PD 缺乏 RBC 表现出糖酵解增加、谷胱甘肽稳态受损和嘌呤氧化增加。此外，在这些途径中，PTR 与特定代谢物之间存在显著相关性。
结论
根据当前 FDA 的标准，来自 G6PD 缺乏供体的 RBC 不符合储存质量要求。代谢组学评估确定了 PTR 和 G6PD 缺乏的标志物（例如，丙酮酸/乳酸比值），以及可能被利用来改善 G6PD 缺乏 RBC 代谢需求的潜在补偿途径。
试验注册
ClinicalTrials.gov NCT04081272。
资助
Harold Amos 医学教师发展计划、Robert Wood Johnson 基金会赠款 71590、国家血液基金会、NIH 赠款 UL1 TR000040、Boettcher 基金会 2017 年 Webb-Waring 早期职业奖、NHLBI 赠款 R01HL14644 和 R01HL148151。
