Department of Neurology, The Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Shijiazhuang, 050000, China.
Key Laboratory of Neurology of Hebei Province, Shijiazhuang, China.
Acta Neurol Belg. 2023 Dec;123(6):2287-2294. doi: 10.1007/s13760-023-02300-3. Epub 2023 Jun 9.
Sirtuin (SIRT)1, as a molecular link between immunity and metabolic pathways, is a key immune response regulator. The significance of SIRT1 in peripheral blood mononuclear cells (PBMCs) of neuromyelitis optica spectrum disorder (NMOSD) has not been investigated. Here, we aimed to evaluate the SIRT1 mRNA level in PBMCs of patients with NMOSD and its clinical relevance and explore the potential mechanism of SIRT1 action.
A total of 65 patients with NMOSD and 60 normal controls from North China were enrolled. Using real-time fluorescence quantitative-polymerase chain reaction, mRNA levels were detected in PBMCs, and protein levels were detected using western blotting.
Compared to the healthy controls and chronic-phase patients with NMOSD, SIRT1 mRNA and protein levels in PBMCs of NMOSD patients with acute attack were significantly downregulated (p < 0.0001). ∆EDSS scores (EDSS scores in the acute phase-EDSS scores before the recent attack) were higher in NMOSD patients with low SIRT1 mRNA level than in patients with high SIRT1 expression (p = 0.042). SIRT1 mRNA level in patients with acute-phase NMSOD was positively correlated with lymphocyte and monocyte counts and negatively correlated with neutrophil counts and the neutrophil-to-lymphocyte ratio. Furthermore, the transcription factor FOXP3 mRNA level was significantly positively correlated with the SIRT1 mRNA level in PBMCs of patients with acute-phase NMOSD.
Our study indicated that SIRT1 mRNA expression was downregulated in the PBMCs of patients with acute-phase NMOSD, and its level was correlated with the clinical parameters of the patients, suggesting a potential role of SIRT1 in NMOSD.
Sirtuin(SIRT)1 作为免疫和代谢途径之间的分子联系,是关键的免疫反应调节剂。SIRT1 在视神经脊髓炎谱系疾病(NMOSD)患者外周血单个核细胞(PBMC)中的意义尚未被研究。在这里,我们旨在评估 NMOSD 患者 PBMC 中的 SIRT1mRNA 水平及其临床相关性,并探讨 SIRT1 作用的潜在机制。
共纳入来自华北地区的 65 名 NMOSD 患者和 60 名正常对照者。采用实时荧光定量聚合酶链反应检测 PBMC 中的 mRNA 水平,采用 Western blot 检测蛋白水平。
与健康对照者和 NMOSD 慢性期患者相比,NMOSD 急性发作期患者 PBMC 中的 SIRT1mRNA 和蛋白水平明显下调(p<0.0001)。SIRT1mRNA 水平较低的 NMOSD 患者的△EDSS 评分(急性期 EDSS 评分-近期发作前的 EDSS 评分)高于 SIRT1 高表达的患者(p=0.042)。急性 NMOSD 患者的 SIRT1mRNA 水平与淋巴细胞和单核细胞计数呈正相关,与中性粒细胞计数和中性粒细胞与淋巴细胞比值呈负相关。此外,急性 NMOSD 患者 PBMC 中的转录因子 FOXP3mRNA 水平与 SIRT1mRNA 水平呈显著正相关。
我们的研究表明,急性 NMOSD 患者 PBMC 中的 SIRT1mRNA 表达下调,其水平与患者的临床参数相关,提示 SIRT1 在 NMOSD 中可能具有潜在作用。