Alterations in the immune landscape characterized by inflammatory activation and immune escape within 12 h after trauma

IF 2.5 4区 医学 Q3 IMMUNOLOGY Immunobiology Pub Date : 2024-04-07 DOI:10.1016/j.imbio.2024.152801
Chenghu Song , Weici Liu , Yu Luo , Jiwei Liu , Guanyu Jiang , Ruixin Wang , Zhao He , Xiaokun Wang , Wenjun Mao
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Abstract

Background

Trauma is statistically a significant cause of mortality among patients across countries. Nevertheless, the precise correlation between genetic diagnostic markers and the intricate mechanism of trauma remains indistinct.

Methods

Our study exclusively centered on trauma patients and selected three trauma-related datasets from the Gene Expression Omnibus (GEO) database, all of which had blood samples collected within post-traumatic 12 h. Differential gene screening, the WGCNA and Cytoscape software were employed to analyze the two datasets, with a particular emphasis on the top 100 genes selected based on MCC algorithm scores. A logistic diagnostic model was constructed by analyzing the intersection genes in the third dataset, leading to the identification of diagnostic biomarkers with high efficiency. The global immune landscape of these patients was extensively investigated using a multidimensional approach. Meanwhile, the underlying pathological and physiological mechanisms associated with early trauma status are summarized by integrating existing literature.

Results

Out of these two GEO datasets, 21 overlapping genes were identified and incorporated into in the logistic diagnostic model constructed in the GSE36809 dataset. A panel of 9 genes was uncovered as a diagnostic biomarker, and their expression and correlation were subsequently verified. Additionally, by virtue of various algorithms, the findings revealed an upregulation of neutrophil expression and a downregulation of CD8+ T cell expression, indicating characteristic early trauma-induced inflammation activation and immune suppression. The correlation observed between the feature genes and immune cells serves to validate the exceptional diagnostic capability of these 9 genes in identifying trauma status and their promising potential for patients who could benefit from targeted immune interventions. Drawing from these findings, the discussion section offers insights into the underlying pathological and physiological mechanisms at play.

Conclusion

Our research has discovered a novel diagnostic biomarker and unveiled its association with post-traumatic immune alterations. This breakthrough enables accurate and timely diagnosis of early trauma, facilitating the implementation of appropriate healthcare interventions.

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创伤后 12 小时内以炎症激活和免疫逃逸为特征的免疫格局变化
背景据统计,创伤是导致各国患者死亡的重要原因之一。方法我们的研究专门以创伤患者为研究对象,从基因表达总库(GEO)数据库中选取了三个创伤相关数据集,所有数据集都采集了创伤后 12 小时内的血液样本。我们采用差异基因筛选、WGCNA 和 Cytoscape 软件对两个数据集进行了分析,重点分析了根据 MCC 算法评分选出的前 100 个基因。通过分析第三个数据集中的交叉基因,构建了一个逻辑诊断模型,从而高效地确定了诊断生物标志物。利用多维方法广泛研究了这些患者的全球免疫景观。结果在这两个 GEO 数据集中,共发现了 21 个重叠基因,并将其纳入到 GSE36809 数据集构建的逻辑诊断模型中。其中有 9 个基因被确定为诊断生物标志物,其表达和相关性随后也得到了验证。此外,通过各种算法,研究结果显示了中性粒细胞表达的上调和 CD8+ T 细胞表达的下调,这表明早期创伤诱导的炎症激活和免疫抑制具有特征性。在特征基因和免疫细胞之间观察到的相关性验证了这 9 个基因在识别创伤状态方面的卓越诊断能力,以及它们对于可能受益于靶向免疫干预的患者的巨大潜力。我们的研究发现了一种新的诊断生物标志物,并揭示了它与创伤后免疫改变的关系。这一突破有助于准确、及时地诊断早期创伤,促进实施适当的医疗干预措施。
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来源期刊
Immunobiology
Immunobiology 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
108
审稿时长
55 days
期刊介绍: Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.
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