培养的淋巴细胞的线粒体基因组完整性不会被克拉德里宾改变
Elina Järvinen1, Fumi Suomi2, James B Stewart3,4
1Merck OY, Espoo, Finland (an affiliate of Merck KGaA, Darmstadt, Germany).
Clinical and experimental immunology
|October 20, 2023
概括
克拉迪宾是一种多发性硬化症治疗方法,不影响线粒体DNA完整性或淋巴细胞中的功能. 这项研究没有发现突变增加,这表明克拉迪宾对淋巴细胞线粒体基因组不致变异.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 克拉德里宾片是一种影响淋巴细胞的多发性硬化症 (MS) 治疗方法,但其确切的机制尚不清楚.
- 了解克拉迪宾对线粒体DNA (mtDNA) 完整性的影响,对于评估其在MS患者的安全性和有效性至关重要.
研究的目的:
- 调查克拉迪宾对线粒体DNA完整性和人类淋巴细胞功能的影响.
- 确定克拉迪宾是否诱导MS患者T细胞系和原发性淋巴细胞的线粒体基因组突变.
主要方法:
- 培养的人类T细胞系 (CCRF-CEM,Jurkat) 用不同度的克拉迪来治疗.
- 来自多发性硬化症患者和对照组的外周血液单核细胞 (PBMC) 用克拉迪宾培养.
- 在淋巴细胞亚群 (CD4+,CD8+,CD19+) 中分析了线粒体DNA拷贝数,蛋白质合成,mRNA突变和体性突变.
主要成果:
- 克拉迪宾并没有影响T细胞系中的线粒体蛋白质合成,mtDNA复制数或cytochrome-c oxidase-I mRNA突变发生.
- 在用克拉德里宾治疗的T细胞系中没有观察到mtDNA突变的显著增加,高达100nM.
- 在MS患者和对照组的克拉迪宾治疗和未治疗的淋巴细胞之间,没有发现mtDNA体变异的差异.
- CD8+和CD4+T细胞表现出比CD19+B细胞更高的mtDNA突变水平,独立于克拉迪宾治疗.
结论:
- 克拉德里宾对淋巴细胞的线粒体基因组没有可检测的突变效应.
- 克拉迪宾在有效度下不会损害人类T细胞系中的线粒体功能.
- 与B细胞相比,T细胞内在具有较高水平的线粒体DNA突变,无论对克拉迪宾的暴露如何.
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