Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium.

Autor:	Reichel F; Max-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany.; Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany., Kräter M; Max-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany.; Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany., Peikert K; Translational Neurodegeneration Section 'Albrecht Kossel', Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany.; Division for Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany., Glaß H; Translational Neurodegeneration Section 'Albrecht Kossel', Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany., Rosendahl P; Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany., Herbig M; Max-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany.; Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany., Rivera Prieto A; Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany., Kihm A; Department of Experimental Physics, Saarland University, Saarbrücken, Germany., Bosman G; Department of Biochemistry, Radboud UMC, Nijmegen, Netherlands., Kaestner L; Department of Experimental Physics, Saarland University, Saarbrücken, Germany.; Theoretical Medicine and Biosciences, Saarland University, Homburg, Germany., Hermann A; Translational Neurodegeneration Section 'Albrecht Kossel', Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany.; Division for Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany.; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Rostock/Greifswald, Rostock, Germany.; Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany., Guck J; Max-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany.; Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2022 Apr 04; Vol. 13, pp. 852946. Date of Electronic Publication: 2022 Apr 04 (Print Publication: 2022).
DOI:	10.3389/fphys.2022.852946
Abstrakt:	Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investigated blood cell deformability of five ChAc patients compared to healthy controls during up to 1-year individual off-label treatment with the tyrosine kinase inhibitor dasatinib or several weeks with lithium. Measurements with two microfluidic techniques allowed us to assess RBC deformability under different shear stresses. Furthermore, we characterized leukocyte stiffness at high shear stresses. The results showed that blood cell deformability-including both RBCs and leukocytes - in general was altered in ChAc patients compared to healthy donors. Therefore, this study shows for the first time an impairment of leukocyte properties in ChAc. During treatment with dasatinib or lithium, we observed alterations in RBC deformability and a stiffness increase for leukocytes. The hematological phenotype of ChAc patients hinted at a reorganization of the cytoskeleton in blood cells which partly explains the altered mechanical properties observed here. These findings highlight the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Reichel, Kräter, Peikert, Glaß, Rosendahl, Herbig, Rivera Prieto, Kihm, Bosman, Kaestner, Hermann and Guck.)
Databáze:	MEDLINE
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