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

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 cell...

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Bibliographic Details
Published in:	Frontiers in physiology Vol. 13; p. 852946
Main Authors:	Reichel, Felix, Kräter, Martin, Peikert, Kevin, Glaß, Hannes, Rosendahl, Philipp, Herbig, Maik, Rivera Prieto, Alejandro, Kihm, Alexander, Bosman, Giel, Kaestner, Lars, Hermann, Andreas, Guck, Jochen
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 04-04-2022
Subjects:	blood cell deformability cell mechanics chorea-acanthocytosis dasatinib lithium Physiology real-time deformability cytometry lithium dasatinib chorea-acanthocytosis real-time deformability cytometry blood cell deformability cell mechanics
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Aljaz Godec, Max Planck Institute for Biophysical Chemistry, Germany This article was submitted to Biophysics, a section of the journal Frontiers in Physiology Asya Makhro, University of Zurich, Switzerland Reviewed by: Yang Jun Kang, Chosun University, South Korea
ISSN:	1664-042X 1664-042X
DOI:	10.3389/fphys.2022.852946