Article (Scientific journals)
The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib.
Rabe, Antonia; Kihm, Alexander; Darras, Alexis et al.
2021In Biomolecules, 11 (5)
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Keywords :
Acanthocytes/drug effects/pathology; Adult; Biomarkers/blood; Blood Sedimentation/drug effects; Cell Shape/drug effects; Dasatinib/therapeutic use; Erythrocytes/drug effects; Humans; Male; Neuroacanthocytosis/blood/drug therapy/pathology; Off-Label Use; Protein Kinase Inhibitors/therapeutic use; 3D shapes; acanthocytes; cell rigidity; dasatinib; erythrocyte sedimentation rate; mesoscopic modeling; microfluidics; phase diagram
Abstract :
[en] BACKGROUND: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. METHODS: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. RESULTS: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. CONCLUSIONS: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rabe, Antonia
Kihm, Alexander
Darras, Alexis
Peikert, Kevin
Simionato, Greta
Dasanna, Anil Kumar
Glaß, Hannes
Geisel, Jürgen
Quint, Stephan
Danek, Adrian
Wagner, Christian ;  University of Luxembourg > Department of Physics and Material Science
Fedosov, Dmitry A.
Hermann, Andreas
Kaestner, Lars
More authors (4 more) Less
External co-authors :
yes
Language :
English
Title :
The Erythrocyte Sedimentation Rate and Its Relation to Cell Shape and Rigidity of Red Blood Cells from Chorea-Acanthocytosis Patients in an Off-Label Treatment with Dasatinib.
Publication date :
2021
Journal title :
Biomolecules
ISSN :
2218-273X
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Volume :
11
Issue :
5
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 06 January 2022

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