循环时钟的干扰损害了慢性内源性高皮质醇症中的免疫振荡:来自多中心临床试验的多层次分析
Valeria Hasenmajer1, Emilia Sbardella1, Francesca Sciarra1
1Department of Experimental Medicine, "Sapienza" University of Rome, Italy.
EBioMedicine
|November 29, 2024
概括
在库辛综合征中,慢性葡萄糖皮质激素过量会破坏免疫细胞节律和时钟基因振荡. 免疫分析有效地识别疾病活动,即使在单个时间点.
科学领域:
- 内分泌学 在内分泌学.
- 时间生物学 时间生物学
- 免疫学 免疫学 免疫学
背景情况:
- 葡萄糖皮质体 (GC) 是关键的昼夜时钟调节者.
- 慢性GC对人类生物节奏的影响仍然未得到充分研究.
- 库辛综合征 (CS) 为持续的GC过量和昼夜干扰提供了一个模型.
研究的目的:
- 为了研究内源性葡萄皮质激素过量对人类昼夜节律的慢性影响.
- 分析周围血液单核细胞 (PBMC) 的每日波动和库辛综合征患者的时钟基因表达.
- 将免疫分析和基因表达与临床参数进行比较,以确定CS活动.
主要方法:
- 一个为期12个月的前性病例控制多中心试验,涉及34名CS患者和34名匹配的对照.
- 分析每日PBMC计数和时钟基因的特定时间表达 (CLOCK,PER1,PER2,PER3,无时间).
- 应用共振或混合效应模型,节奏算法和机器学习技术.
主要成果:
- 活跃的CS显示了PBMC水平,振幅和节律的深刻变化,缓解后部分恢复.
- 关键时钟基因的循环节振荡在CS患者的PBMC中显著平坦,与对照组相比失去节律性.
- 机器学习确定免疫分析比皮质醇,代谢变量和检测CS活动的基因表达优越.
结论:
- 循环免疫细胞振荡在库辛综合征中显著改变,将昼夜干扰与荷尔蒙失衡联系起来.
- 这项研究强调了中断的昼夜节律和CS中的类固醇激素过量趋同.
- 与其他临床和分子标记物相比,免疫细胞分析在识别活性CS方面表现出更高的有效性.
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