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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Felix Reichel - , Professur für Zelluläre Netzwerke und Systeme, Fakultät Physik, Max Planck Institute for the Science of Light (Autor:in)
  • Martin Kräter - , Max Planck Institute for the Science of Light, Technische Universität Dresden (Autor:in)
  • Kevin Peikert - , Institut für Anatomie, Universitätsmedizin Rostock, Universität Rostock, Division for Neurodegenerative Diseases, Technische Universität Dresden (Autor:in)
  • Hannes Glaß - , Universität Rostock (Autor:in)
  • Philipp Rosendahl - , Fakultät Physik, Technische Universität Dresden (Autor:in)
  • Maik Herbig - , Fakultät Physik, Max Planck Institute for the Science of Light, Technische Universität Dresden (Autor:in)
  • Alejandro Rivera Prieto - , Technische Universität Dresden (Autor:in)
  • Alexander Kihm - , Universität des Saarlandes (Autor:in)
  • Giel Bosman - , Radboud University Nijmegen (Autor:in)
  • Lars Kaestner - , Universität des Saarlandes (Autor:in)
  • Andreas Hermann - , Universität Rostock, Technische Universität Dresden, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) (Autor:in)
  • Jochen Guck - , Professur für Zelluläre Maschinen, Max Planck Institute for the Science of Light (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummer852946
FachzeitschriftFrontiers in physiology
Jahrgang13
PublikationsstatusVeröffentlicht - 4 Apr. 2022
Peer-Review-StatusJa

Schlagworte

Schlagwörter

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