López-Cruz Ian, García-Giménez José Luis, Madrazo Manuel, García-Guallarte Judit, Piles Laura, Pallardó Federico V, Artero Arturo
Department of Internal Medicine, Dr. Peset University Hospital, Valencia, Spain.
Department of Medicine, Faculty of Medicine & Dentistry, University of Valencia, Valencia, Spain.
Front Cell Infect Microbiol. 2025 Jan 24;14:1532417. doi: 10.3389/fcimb.2024.1532417. eCollection 2024.
Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis.
A prospective case-control study was conducted to compare DNA methylation profiles between patients with community-acquired sepsis and matched controls who had similar infections but did not develop sepsis. Whole blood samples from these patients were analyzed using the Infinium MethylationEPIC v2.0 kit, enabling genome-wide methylation analysis. Selected genes with differential methylation were validated by pyrosequencing.
Significant differential DNA methylation patterns were identified between septic and non-septic individuals uising. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction. The most prominent findings include the hypomethylation of immune-related genes (, and ), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels. Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858).
Our results underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.
脓毒症是一种由对感染的免疫反应失调引起的危及生命的病症，可导致器官衰竭。尽管其在全球造成了重大负担，但脓毒症中免疫功能障碍的潜在机制仍未完全了解。本研究探讨DNA甲基化在脓毒症发病机制中白细胞中的作用。
进行了一项前瞻性病例对照研究，以比较社区获得性脓毒症患者与具有相似感染但未发生脓毒症的匹配对照之间的DNA甲基化谱。使用Infinium MethylationEPIC v2.0试剂盒分析这些患者的全血样本，从而实现全基因组甲基化分析。通过焦磷酸测序验证选定的甲基化差异基因。
在脓毒症患者和非脓毒症个体之间鉴定出显著的DNA甲基化差异模式。我们的结果表明，DNA甲基化变化与脓毒症的病理生理过程密切相关，影响免疫细胞活化、炎症和器官功能障碍。最显著的发现包括免疫相关基因（ 、 和 ）的低甲基化，这些基因与临床严重程度和炎症标志物如序贯器官衰竭评估（SOFA）评分和降钙素原（PCT）水平密切相关。相关性分析表明这些基因的甲基化水平与临床严重程度标志物之间存在显著关联，如SOFA评分和PCT水平。值得注意的是， 基因低甲基化对预后不良具有最高的预测价值（曲线下面积[AUC]为0.821），而 基因低甲基化对脓毒症具有很强的诊断潜力（AUC为0.858）。
我们的结果强调了DNA甲基化变化的潜力，特别是在免疫相关基因中，可提高脓毒症的早期检测并根据严重程度对患者进行分层。未来的研究应探索这些表观遗传改变在脓毒症治疗中的意义。
