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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Felix Reichel - , Chair of Cellular Circuits and Systems, Faculty of Physics, Max Planck Institute for the Science of Light (Author)
  • Martin Kräter - , Max Planck Institute for the Science of Light, TUD Dresden University of Technology (Author)
  • Kevin Peikert - , Institute of Anatomy, Rostock University Medical Centre, University of Rostock, Division for Neurodegenerative Diseases, TUD Dresden University of Technology (Author)
  • Hannes Glaß - , University of Rostock (Author)
  • Philipp Rosendahl - , Faculty of Physics, TUD Dresden University of Technology (Author)
  • Maik Herbig - , Faculty of Physics, Max Planck Institute for the Science of Light, TUD Dresden University of Technology (Author)
  • Alejandro Rivera Prieto - , TUD Dresden University of Technology (Author)
  • Alexander Kihm - , Saarland University (Author)
  • Giel Bosman - , Radboud University Nijmegen (Author)
  • Lars Kaestner - , Saarland University (Author)
  • Andreas Hermann - , University of Rostock, TUD Dresden University of Technology, German Center for Neurodegenerative Diseases (DZNE) (Author)
  • Jochen Guck - , Chair of Cellular Machines, Max Planck Institute for the Science of Light (Author)

Abstract

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.

Details

Original languageEnglish
Article number852946
JournalFrontiers in physiology
Volume13
Publication statusPublished - 4 Apr 2022
Peer-reviewedYes

Keywords

ASJC Scopus subject areas

Keywords

  • blood cell deformability, cell mechanics, chorea-acanthocytosis, dasatinib, lithium, real-time deformability cytometry