AUTHOR=Anastasiadi Alkmini T. , Tzounakas Vassilis L. , Dzieciatkowska Monika , Arvaniti Vasiliki-Zoi , Papageorgiou Effie G. , Papassideri Issidora S. , Stamoulis Konstantinos , D’Alessandro Angelo , Kriebardis Anastasios G. , Antonelou Marianna H. 

TITLE=Innate Variability in Physiological and Omics Aspects of the Beta Thalassemia Trait-Specific Donor Variation Effects

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.907444

DOI=10.3389/fphys.2022.907444

ISSN=1664-042X

ABSTRACT=<p>The broad spectrum of beta-thalassemia (<italic>β</italic>Thal) mutations may result in mild reduction (<italic>β</italic><sup>++</sup>), severe reduction (<italic>β</italic><sup>+</sup>) or complete absence (<italic>β</italic><sup>0</sup>) of beta-globin synthesis. <italic>β</italic>Thal heterozygotes eligible for blood donation are “good storers” in terms of red blood cell (RBC) fragility, proteostasis and redox parameters of storage lesion. However, it has not been examined if heterogeneity in genetic backgrounds among <italic>β</italic>Thal-trait donors affects their RBC storability profile. For this purpose, a paired analysis of physiological and omics parameters was performed in freshly drawn blood and CPD/SAGM-stored RBCs donated by eligible volunteers of <italic>β</italic><sup>++</sup> (N = 4), <italic>β</italic><sup>+</sup> (N = 9) and <italic>β</italic><sup>0</sup> (N = 2) mutation-based phenotypes. Compared to <italic>β</italic><sup>+</sup>, <italic>β</italic><sup>++</sup> RBCs were characterized by significantly lower RDW and HbA<sub>2</sub> but higher hematocrit, MCV and NADPH levels <italic>in vivo</italic>. Moreover, they had lower levels of reactive oxygen species and markers of oxidative stress, already from baseline. Interestingly, their lower myosin and arginase membrane levels were accompanied by increased cellular fragility and arginine values. Proteostasis markers (proteasomal activity and/or chaperoning-protein membrane-binding) seem to be also diminished in <italic>β</italic><sup>++</sup> as opposed to the other two phenotypic groups. Overall, despite the low number of samples in the sub-cohorts, it seems that the second level of genetic variability among the group of βThal-trait donors is reflected not only in the physiological features of RBCs <italic>in vivo</italic>, but almost equally in their storability profiles. Mutations that only slightly affect the globin chain equilibrium direct RBCs towards phenotypes closer to the average control, at least in terms of fragility indices and proteostatic dynamics.</p>