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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.852946/full |
| _version_ | 1811311531811405824 |
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| author | Felix Reichel Felix Reichel Martin Kräter Martin Kräter Kevin Peikert Kevin Peikert Hannes Glaß Philipp Rosendahl Maik Herbig Maik Herbig Alejandro Rivera Prieto Alexander Kihm Giel Bosman Lars Kaestner Lars Kaestner Andreas Hermann Andreas Hermann Andreas Hermann Andreas Hermann Jochen Guck Jochen Guck |
| author_facet | Felix Reichel Felix Reichel Martin Kräter Martin Kräter Kevin Peikert Kevin Peikert Hannes Glaß Philipp Rosendahl Maik Herbig Maik Herbig Alejandro Rivera Prieto Alexander Kihm Giel Bosman Lars Kaestner Lars Kaestner Andreas Hermann Andreas Hermann Andreas Hermann Andreas Hermann Jochen Guck Jochen Guck |
| author_sort | Felix Reichel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T10:20:38Z |
| format | Article |
| id | doaj.art-645ea33f20b14c928418de3cbbbf3408 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-13T10:20:38Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-645ea33f20b14c928418de3cbbbf34082022-12-22T02:50:31ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-04-011310.3389/fphys.2022.852946852946Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or LithiumFelix Reichel0Felix Reichel1Martin Kräter2Martin Kräter3Kevin Peikert4Kevin Peikert5Hannes Glaß6Philipp Rosendahl7Maik Herbig8Maik Herbig9Alejandro Rivera Prieto10Alexander Kihm11Giel Bosman12Lars Kaestner13Lars Kaestner14Andreas Hermann15Andreas Hermann16Andreas Hermann17Andreas Hermann18Jochen Guck19Jochen Guck20Max-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, GermanyBiotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, GermanyMax-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, GermanyBiotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, GermanyTranslational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, GermanyDivision for Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, GermanyTranslational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, GermanyBiotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, GermanyMax-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, GermanyBiotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, GermanyBiotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, GermanyDepartment of Experimental Physics, Saarland University, Saarbrücken, GermanyDepartment of Biochemistry, Radboud UMC, Nijmegen, NetherlandsDepartment of Experimental Physics, Saarland University, Saarbrücken, GermanyTheoretical Medicine and Biosciences, Saarland University, Homburg, GermanyTranslational Neurodegeneration Section “Albrecht Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, GermanyDivision for Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, GermanyDeutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Rostock/Greifswald, Rostock, GermanyCenter for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, GermanyMax-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, GermanyBiotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, GermanyMisshaped 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.https://www.frontiersin.org/articles/10.3389/fphys.2022.852946/fullchorea-acanthocytosisblood cell deformabilityreal-time deformability cytometrydasatiniblithiumcell mechanics |
| spellingShingle | Felix Reichel Felix Reichel Martin Kräter Martin Kräter Kevin Peikert Kevin Peikert Hannes Glaß Philipp Rosendahl Maik Herbig Maik Herbig Alejandro Rivera Prieto Alexander Kihm Giel Bosman Lars Kaestner Lars Kaestner Andreas Hermann Andreas Hermann Andreas Hermann Andreas Hermann Jochen Guck Jochen Guck Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium Frontiers in Physiology chorea-acanthocytosis blood cell deformability real-time deformability cytometry dasatinib lithium cell mechanics |
| title | Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium |
| title_full | Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium |
| title_fullStr | Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium |
| title_full_unstemmed | Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium |
| title_short | Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium |
| title_sort | changes in blood cell deformability in chorea acanthocytosis and effects of treatment with dasatinib or lithium |
| topic | chorea-acanthocytosis blood cell deformability real-time deformability cytometry dasatinib lithium cell mechanics |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.852946/full |
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