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
Antonia Rabe,
Alexander Kihm,
Alexis Darras,
Kevin Peikert,
Greta Simionato,
Anil Kumar Dasanna,
Hannes Glaß,
Jürgen Geisel,
Stephan Quint,
Adrian Danek,
Christian Wagner,
Dmitry A. Fedosov,
Andreas Hermann,
Lars Kaestner
Affiliations
Antonia Rabe
Theoretical Medicine and Biosciences, Saarland University, 66424 Homburg, Germany
Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18051 Rostock, Germany
Institute of Biological Information Processing and Institute for Advanced Simulation, Forschungszentrum Jülich, 52425 Jülich, Germany
Hannes Glaß
Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18051 Rostock, Germany
Jürgen Geisel
Central Laboratory, Saarland University Medical Centre, 66424 Homburg, Germany
Institute of Biological Information Processing and Institute for Advanced Simulation, Forschungszentrum Jülich, 52425 Jülich, Germany
Andreas Hermann
Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18051 Rostock, Germany
Lars Kaestner
Theoretical Medicine and Biosciences, Saarland University, 66424 Homburg, Germany
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.
