Density, heterogeneity and deformability of red cells as markers of clinical severity in hereditary spherocytosis
Huisjes, R. (Department of Clinical Chemistry and Hematology. University Medical Center Utrecht. Utrecht University)
Makhro, A. (Red Blood Cell Research Group. Institute of Veterinary Physiology. Vetsuisse Faculty. Zurich Center for Integrative Human Physiology (ZIHP). University of Zurich)
Llaudet-Planas, Esther (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Hertz, L. (Theoretical Medicine and Biosciences. Medical Faculty. Saarland University)
Petkova-Kirova, P. (Theoretical Medicine and Biosciences. Medical Faculty. Saarland University)
Verhagen, L. P. (Department of Clinical Chemistry and Hematology. University Medical Center Utrecht. Utrecht University)
Pignatelli, S. (Department of Clinical Chemistry and Hematology. University Medical Center Utrecht. Utrecht University)
Rab, M. A. E. (Department of Clinical Chemistry and Hematology. University Medical Center Utrecht. Utrecht University)
Schiffelers, Raymond M. (Department of Clinical Chemistry and Hematology. University Medical Center Utrecht. Utrecht University)
Seiler, E. (Red Blood Cell Research Group. Institute of Veterinary Physiology. Vetsuisse Faculty. Zurich Center for Integrative Human Physiology (ZIHP). University of Zurich)
Van Solinge, W. W. (Department of Clinical Chemistry and Hematology. University Medical Center Utrecht. Utrecht University)
Vives Corrons, Juan Luís (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Kaestner, L. (Experimental Physics. Saarland University)
Mañú Pereira, María del Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bogdanov, A. (Red Blood Cell Research Group. Institute of Veterinary Physiology. Vetsuisse Faculty. Zurich Center for Integrative Human Physiology (ZIHP). University of Zurich)
Van Wijk, R. (Department of Clinical Chemistry and Hematology. University Medical Center Utrecht. Utrecht University)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	Hereditary spherocytosis (HS) originates from defective anchoring of the cytoskeletal network to the transmembrane protein complexes of the red blood cell (RBC). Red cells in HS are characterized by membrane instability and reduced deformability and there is marked heterogeneity in disease severity among patients. To unravel this variability in disease severity, we analyzed blood samples from 21 HS patients with defects in ankyrin, band 3, á-spectrin or β-spectrin using red cell indices, eosin-5- maleimide binding, microscopy, the osmotic fragility test, Percoll density gradients, vesiculation and ektacytometry to assess cell membrane stability, cellular density and deformability. Reticulocyte counts, CD71 abundance, band 4. 1 a:b ratio, and glycated hemoglobin were used as markers of RBC turnover. We observed that patients with moderate/severe spherocytosis have short-living erythrocytes of low density and abnormally high intercellular heterogeneity. These cells show a prominent decrease in membrane stability and deformability and, as a consequence, are quickly removed from the circulation by the spleen. In contrast, in mild spherocytosis less pronounced reduction in deformability results in prolonged RBC lifespan and, hence, cells are subject to progressive loss of membrane. RBC from patients with mild spherocytosis thus become denser before they are taken up by the spleen. Based on our findings, we conclude that RBC membrane loss, cellular heterogeneity and density are strong markers of clinical severity in spherocytosis.
Ajuts:	European Commission 675115 European Commission 602121
Nota:	Altres ajuts: This work was generated within the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet) - FPA No. 739541
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Haematologica, Vol. 105 Núm. 2 (31 2020) , p. 338-347, ISSN 1592-8721

DOI: 10.3324/haematol.2018.188151
PMID: 31147440

10 p, 1.8 MB

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