Objectives: The aim of this study wasto investigate the efficacy of tacrolimus treatment in patients with refractory generalized myasthenia gravis (MG) and explore its impact on lymphocytic phenotypes and related cytokines mRNA expression. Methods: A total of 24 refractory generalized MG patients were enrolled. Before treatment and at 2, 6, and 12 months after tacrolimus treatment, the therapeutic effect was evaluated by the quantitative MG score of the Myasthenia Gravis Foundation of America (QMG), Manual Muscle Test (MMT), MG-specific Activities of Daily Living (MG-ADL), 15-item Myasthenia Gravis Quality-of-Life Scale (MG-QOL15), and changes of prednisone dosage. Also, we used the flow cytometer for the lymphocytic immunophenotyping and real-time PCR for the qualification of cytokine mRNA in peripheral blood mononuclear cells (PBMCs) at different time points during the treatment. Results: Significantly decreased QMG, MMT, MG-ADL, and MG-QOL15 were observed at all time points during the tacrolimus treatment. The dosage of prednisone also reduced at the end of the observation period with only 6 adverse events reported. The immunological impact of tacrolimus was revealed by reduced percentages of Tfh, Breg, CD19+BAFF-R+ B cells, and increased percentages of Treg cells as well as down-regulated expression of IL-2, IL-4, IL-10, and IL-13 mRNA levels in PBMCs during the treatment. Conclusion: Our study indicated the clinical efficacy of tacrolimus in patients with refractory generalized MG. The underlying immunoregulatory mechanism of tacrolimus may involve alterations in the phenotypes of peripheral blood lymphocytes and Th1/Th2-related cytokine expression of PBMCs.

中文翻译：

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他克莫司对难治性全身性重症肌无力患者的治疗和免疫调节作用

目的：本研究旨在探讨他克莫司治疗难治性全身性重症肌无力（MG）患者的疗效，并探讨其对淋巴细胞表型和相关细胞因子 mRNA 表达的影响。方法：共纳入 24 例难治性全身 MG 患者。治疗前及他克莫司治疗后2、6、12个月时，通过美国重症肌无力基金会（QMG）的定量MG评分、手动肌肉测试（MMT）、MG特异性日常生活活动量评估疗效(MG-ADL)、15 项重症肌无力生活质量量表 (MG-QOL15) 和泼尼松剂量的变化。还，我们使用流式细胞仪进行淋巴细胞免疫表型分析，并使用实时 PCR 对治疗期间不同时间点的外周血单核细胞 (PBMC) 中的细胞因子 mRNA 进行鉴定。结果：在他克莫司治疗期间的所有时间点均观察到 QMG、MMT、MG-ADL 和 MG-QOL15 显着降低。在观察期结束时，泼尼松的剂量也有所减少，仅报告了 6 起不良事件。他克莫司的免疫学影响通过降低 Tfh、Breg、CD1​​9+BAFF-R+ B 细胞百分比和增加 Treg 细胞百分比以及下调 IL-2、IL-4、IL-10 和治疗期间 PBMC 中的 IL-13 mRNA 水平。结论：我们的研究表明他克莫司对难治性全身 MG 患者的临床疗效。