阻塞性睡眠呼吸暂停综合征（OSAS）患者外周单个核细胞代谢组学：免疫代谢特征的探索性初步研究

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中文摘要

阻塞性睡眠呼吸暂停综合征（OSAS）与全身性炎症和免疫功能障碍相关，但免疫细胞内的具体代谢改变仍知之甚少。在这项探索性研究中，我们表征了OSAS患者和健康对照者外周单个核细胞（PMNCs）的代谢组，以探究与该疾病相关的潜在免疫代谢特征。初步分析鉴定出OSAS患者与对照者之间21种名义上差异丰度的代谢物，提示肉碱耗竭以及脂肪酸和神经递质代谢改变等趋势。然而，经多重检验校正（错误发现率，FDR）后，仅推定注释的顺,顺-粘康酸仍具有统计学显著性。此外，通路富集分析突出了主要与SLC介导的跨膜转运和能量代谢相关的探索性趋势。我们的研究结果表明，虽然OSAS患者的PMNCs表现出提示细胞应激的代谢变化，但其中大多数改变代表名义趋势，需要在更大队列中验证。对推定注释的顺,顺-粘康酸的稳健鉴定突出了一个潜在关注靶点。在这项探索性初步研究中，鉴于大多数参与者缺乏多导睡眠图和客观缺氧参数，所观察到的代谢改变被描述为与间歇性缺氧相关，而非由间歇性缺氧直接引起。总体而言，本研究为未来关于OSAS免疫代谢后果的研究提供了一个产生假设的框架。

英文摘要

Obstructive Sleep Apnea Syndrome (OSAS) is associated with systemic inflammation and immune dysfunction, yet the specific metabolic alterations within immune cells remain poorly understood. In this exploratory study, we characterized the metabolome of peripheral mononuclear cells (PMNCs) from patients with OSAS and healthy controls to investigate potential immunometabolic signatures associated with the disease. Initial analyses identified 21 nominally differentially abundant metabolites between OSAS patients and controls, suggesting trends such as the depletion of carnitines and alterations in fatty acid and neurotransmitter metabolism. However, following correction for multiple testing (False Discovery Rate, FDR), only putatively annotated cis,cis-muconic acid remained statistically significant. Furthermore, pathway enrichment analysis highlighted exploratory trends primarily associated with SLC-mediated transmembrane transport and energy metabolism. Our findings indicate that while OSAS PMNCs exhibit metabolic shifts suggestive of cellular stress, most of these alterations represent nominal trends that require validation in larger cohorts. The robust identification of putatively annotated cis,cis-muconic acid highlights a potential target of interest. In this exploratory pilot study, given the absence of polysomnographic and objective hypoxia parameters in most participants, observed metabolic alterations are described as associated with, rather than directly caused by, intermittent hypoxia. Overall, this study provides a hypothesis-generating framework for future research on the immunometabolic consequences of OSAS.