Vinkel Julie, Buil Alfonso, Hyldegaard Ole
Department of Anaesthesiology, Centre of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Inge Lehmanns Vej 6, Copenhagen, 2100, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
BMC Med Genomics. 2025 Jan 14;18(1):12. doi: 10.1186/s12920-024-02075-3.
Sepsis and shock are common complications of necrotising soft tissue infections (NSTI). Sepsis encompasses different endotypes that are associated with specific immune responses. Hyperbaric oxygen (HBO) treatment activates the cells oxygen sensing mechanisms that are interlinked with inflammatory pathways. We aimed to identify gene expression patterns associated with effects of HBO treatment in patients with sepsis caused by NSTI, and to explore sepsis-NSTI profiles that are more receptive to HBO treatment.
An observational cohort study examining 83 NSTI patients treated with HBO in the acute phase of NSTI, fourteen of whom had received two sessions of HBO (HBOx2 group), and another ten patients (non-HBO group) who had not been exposed to HBO. Whole blood RNA sequencing and clinical data were collected at baseline and after the intervention, and at equivalent time points in the non-HBO group. Gene expression profiles were analysed using machine learning techniques to identify sepsis endotypes, treatment response endotypes and clinically relevant transcriptomic signatures of response to treatment.
We identified differences in gene expression profiles at follow-up between HBO-treated patients and patients not treated with HBO. Moreover, we identified two patient endotypes before and after treatment that represented an immuno-suppressive and an immune-adaptive endotype respectively, and we characterized the genetic profile of the patients that transition from the immuno-suppressive to the immune-adaptive endotype after treatment. We discovered one gene MTCO2P12 that distinguished individuals who altered their endotype in response to treatment from non-responders.
The global gene expression pattern in blood changed in response to HBO treatment in a direction associated with clinical biochemistry improvement, and the study provides potential novel biomarkers and pathways for monitoring HBO treatment effects and predicting an HBO responsive NSTI-sepsis profile.
Biological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698) 04/02/2013.
脓毒症和休克是坏死性软组织感染（NSTI）的常见并发症。脓毒症包含与特定免疫反应相关的不同内型。高压氧（HBO）治疗可激活与炎症途径相互关联的细胞氧感应机制。我们旨在确定与HBO治疗对NSTI所致脓毒症患者的影响相关的基因表达模式，并探索对HBO治疗更敏感的脓毒症-NSTI特征。
一项观察性队列研究，纳入83例在NSTI急性期接受HBO治疗的患者，其中14例接受了两个疗程的HBO治疗（HBOx2组），另外10例患者（非HBO组）未接受HBO治疗。在基线、干预后以及非HBO组的等效时间点收集全血RNA测序和临床数据。使用机器学习技术分析基因表达谱，以确定脓毒症内型、治疗反应内型以及治疗反应的临床相关转录组特征。
我们发现接受HBO治疗的患者与未接受HBO治疗的患者在随访时基因表达谱存在差异。此外，我们确定了治疗前后的两种患者内型，分别代表免疫抑制内型和免疫适应内型，并对治疗后从免疫抑制内型转变为免疫适应内型的患者的基因特征进行了描述。我们发现一个基因MTCO2P12，它可区分对治疗有内型改变的个体与无反应者。
血液中的整体基因表达模式因HBO治疗而发生变化，且变化方向与临床生化指标改善相关，该研究为监测HBO治疗效果和预测对HBO有反应的NSTI-脓毒症特征提供了潜在的新型生物标志物和途径。
生物材料在INFECT研究期间收集，该研究于2013年2月4日在ClinicalTrials.gov注册（NCT01790698）。
