MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Ashton Street, Liverpool L69 3GE, U.K.
Otsuka Pharmaceutical Development & Commercialization, Inc., Research Boulevard, Rockville, Maryland 20882, United States.
Chem Res Toxicol. 2020 Nov 16;33(11):2745-2748. doi: 10.1021/acs.chemrestox.0c00328. Epub 2020 Oct 21.
Tolvaptan is an effective drug for the treatment of autosomal dominant polycystic kidney disease, but its use is associated with a significant risk of liver injury in a small number of patients. Herein we describe the presence of tolvaptan- and tolvaptan-metabolite-responsive T cell clones within the peripheral circulation of patients with liver injury. Drug treatment of the clones resulted in a proliferative response and secretion of IFN-γ, IL-13, and the cytolytic molecule granzyme B. Future work should explore pathways of tolvaptan driven T cell activation and the role of T cells in the disease pathogenesis.
托伐普坦是治疗常染色体显性遗传多囊肾病的有效药物,但它在少数患者中使用与肝损伤的风险显著相关。本文描述了肝损伤患者外周循环中存在托伐普坦和托伐普坦代谢物反应性 T 细胞克隆。药物治疗这些克隆导致增殖反应和 IFN-γ、IL-13 和细胞毒性分子颗粒酶 B 的分泌。未来的工作应该探索托伐普坦驱动 T 细胞激活的途径以及 T 细胞在疾病发病机制中的作用。