Reichel Felix, Kräter Martin, Peikert Kevin, Glaß Hannes, Rosendahl Philipp, Herbig Maik, Rivera Prieto Alejandro, Kihm Alexander, Bosman Giel, Kaestner Lars, Hermann Andreas, Guck Jochen
Max-Planck-Institut für die Physik des Lichts and Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany.
Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany.
Front Physiol. 2022 Apr 4;13:852946. doi: 10.3389/fphys.2022.852946. eCollection 2022.
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.
畸形红细胞（RBCs），其特征是具有称为棘形红细胞的刺状突起，是舞蹈病 - 棘红细胞增多症（ChAc）这一罕见神经退行性疾病的关键诊断特征。红细胞形态的改变可能会影响其生物力学特性，而这些特性对于细胞通过微血管至关重要。在此，我们研究了5名ChAc患者与健康对照者在长达1年的酪氨酸激酶抑制剂达沙替尼个体化非标签治疗期间或锂治疗数周后的血细胞变形性。使用两种微流控技术进行测量使我们能够评估不同剪切应力下的红细胞变形性。此外，我们还表征了高剪切应力下白细胞的硬度。结果表明，与健康供体相比，ChAc患者的血细胞变形性（包括红细胞和白细胞）总体上发生了改变。因此，本研究首次表明ChAc患者存在白细胞特性受损。在使用达沙替尼或锂治疗期间，我们观察到红细胞变形性的改变以及白细胞硬度的增加。ChAc患者的血液学表型提示血细胞中细胞骨架的重组，这部分解释了此处观察到的机械特性改变。这些发现凸显了系统评估血细胞力学受损对ChAc临床表现的贡献的必要性。
