Klinik und Poliklinik für Neurologie, University of Leipzig, 04103 Leipzig, Germany.
Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany.
Int J Mol Sci. 2024 Aug 15;25(16):8883. doi: 10.3390/ijms25168883.
Multiple sclerosis (MS) is associated with alterations in neuroendocrine function, primarily the hypothalamic-pituitary-adrenal axis, including lower expression of the glucocorticoid receptor (GR) and its target genes in peripheral blood mononuclear cells (PBMC) or full blood. We previously found reduced mineralocorticoid receptor (MR) expression in MS patients' peripheral blood. MS is being treated with a widening variety of disease-modifying treatments (DMT), some of which have similar efficacy but different mechanisms of action; body-fluid biomarkers to support the choice of the optimal initial DMT and/or to indicate an unsatisfactory response before clinical activity are unavailable. Using cell culture of volunteers' PBMCs and subsequent gene expression analysis (microarray and qPCR validation), we identified the mRNA expression of OTUD1 to represent MR signaling. The MR and MR target gene expression levels were then measured in full blood samples. In 119 MS (or CIS) patients, the expression of both MR and OTUD1 was lower than in 42 controls. The expression pattern was related to treatment, with the MR expression being particularly low in patients treated with fingolimod. While MR signaling may be involved in the therapeutic effects of some disease-modifying treatments, MR and OTUD1 expression can complement the neuroendocrine assessment of MS disease course. If confirmed, such assessment may support clinical decision-making.
多发性硬化症 (MS) 与神经内分泌功能改变有关，主要是下丘脑-垂体-肾上腺轴，包括外周血单个核细胞 (PBMC) 或全血中糖皮质激素受体 (GR) 及其靶基因的表达降低。我们之前发现 MS 患者外周血中的矿物质皮质激素受体 (MR) 表达减少。MS 采用越来越多种类的疾病修正治疗 (DMT) 进行治疗，其中一些具有相似的疗效但作用机制不同；目前还没有体液生物标志物来支持选择最佳初始 DMT 和/或在临床活动前提示治疗反应不佳。我们使用志愿者 PBMC 的细胞培养和随后的基因表达分析（微阵列和 qPCR 验证），确定 OTUD1 的 mRNA 表达代表 MR 信号。然后在全血样本中测量 MR 和 MR 靶基因的表达水平。在 119 名 MS（或 CIS）患者中，MR 和 OTUD1 的表达均低于 42 名对照者。表达模式与治疗有关，在用芬戈莫德治疗的患者中，MR 表达特别低。虽然 MR 信号可能参与一些疾病修正治疗的治疗效果，但 MR 和 OTUD1 的表达可以补充 MS 疾病过程的神经内分泌评估。如果得到证实，这种评估可能支持临床决策。
