Donor sex, age and ethnicity impact stored red blood cell antioxidant metabolism through mechanisms in part explained by glucose 6-phosphate dehydrogenase levels and activity

Red blood cell storage in the blood bank promotes the progressive accumulation of metabolic alterations that may ultimately impact the erythrocyte capacity to cope with oxidant stressors. However, the metabolic underpinnings of the capacity of RBCs to resist oxidant stress and the potential impact o...

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Published inHaematologica (Roma) Vol. 106; no. 5; pp. 1290 - 1302
Main Authors D'Alessandro, Angelo, Fu, Xiaoyun, Kanias, Tamir, Reisz, Julie A, Culp-Hill, Rachel, Guo, Yuelong, Gladwin, Mark T, Page, Grier, Kleinman, Steven, Lanteri, Marion, Stone, Mars, Busch, Michael P, Zimring, James C
Format Journal Article
LanguageEnglish
Published Italy Fondazione Ferrata Storti 01.05.2021
Ferrata Storti Foundation
Subjects
Adult
Antioxidants
Blood Preservation
Erythrocytes
Ethnicity
Female
Glucose
Glucosephosphate Dehydrogenase - genetics
Hemolysis
Humans
Male
Middle Aged
Phosphates
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Summary:Red blood cell storage in the blood bank promotes the progressive accumulation of metabolic alterations that may ultimately impact the erythrocyte capacity to cope with oxidant stressors. However, the metabolic underpinnings of the capacity of RBCs to resist oxidant stress and the potential impact of donor biology on this phenotype are not known. Within the framework of the REDS-III RBC-Omics study, RBCs from 8,502 healthy blood donors were stored for 42 days and tested for their propensity to hemolyze following oxidant stress. A subset of extreme hemolyzers donated a second unit of blood, which was stored for 10, 23, and 42 days and profiled again for oxidative hemolysis and metabolomics (599 samples). Alterations of RBC energy and redox homeostasis were noted in donors with high oxidative hemolysis. RBCs from females, donors over 60 years old, donors of Asian/South Asian race-ethnicity, and RBCs stored in additive solution-3 were each independently characterized by improved antioxidant metabolism compared to, respectively, males, donors under 30 years old, Hispanic and African American race ethnicity donors, and RBCs stored in additive solution-1. Merging metabolomics data with results from an independent GWAS study on the same cohort, we identified metabolic markers of hemolysis and G6PD-deficiency, which were associated with extremes in oxidative hemolysis and dysregulation in NADPH and glutathione-dependent detoxification pathways of oxidized lipids. Donor sex, age, ethnicity, additive solution and G6PD status impact the metabolism of the stored erythrocyte and its susceptibility to hemolysis following oxidative insults.
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RBC-Omics study group members
Disclosures
Though unrelated to the contents of this manuscripts, the authors declare that AD is a founder of Omix Technologies Inc and Altis Biosciencens LLC. James C Zimring serves as a consultant for Rubius Therapeutics. All the other authors disclose no conflicts of interest relevant to this study. Angelo D’Alessandro is a consultant for Hemanext Inc. James C Zimring serves on the scientific advisory board for Rubius Therapeutics. All the other authors disclose no conflicts of interest relevant to this study.
Contributions
TK, SK, MTG, ML, MS, MPB, GP, JCZ designed the study. AD, XF, JAR, RCH, JCZ performed metabolomics analyses; YG, GP performed genomics analyses; TK performed oxidative hemolysis measurements; AD prepared figures and wrote the first version of the manuscript. All the authors contributed to the finalization of the manuscript.
The NHLBI Recipient Epidemiology Donor Evaluation Study- III (REDS-III), Red Blood Cell (RBC)-Omics study, is the responsibility of the following persons: Hubs: AE Mast, JL Gottschall, WB, LA, JM, AH, ZU, and VJ, BloodCenter of Wisconsin, Milwaukee, WI, USA; DJT, JEK and PAD’A, The Institute for Transfusion Medicine (ITXM), Pittsburgh, PA, USA; E. L. Murphy and AMG, University of California, San Francisco, San Francisco, CA, USA; RGC, BRS, and STJ; American Red Cross Blood Services, Farmington, CT, USA; Data coordinating center: DJB, MTS, SME, GPP, YG, NH, DR, and BCS; RTI International, Rockville, MD, USA; Central and testing laboratories: MPB, MCL, MS, and SK, Blood Systems Research Institute, San Francisco, CA, USA; TK and MG, Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Steering committee chairman: SHK, University of British Columbia, Victoria, BC, Canada; National Heart, Lung, and Blood Institute, National Institutes of Health: SAG, KBM and AMC.
ISSN:0390-6078
1592-8721
1592-8721
DOI:10.3324/haematol.2020.246603