常规和非常规 T 细胞反应有助于预测脓毒症患者的临床结果和致病细菌病原体。

Conventional and unconventional T-cell responses contribute to the prediction of clinical outcome and causative bacterial pathogen in sepsis patients.

机构信息

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.

Adult Critical Care, University Hospital of Wales, Cardiff and Vale University Health Board, Cardiff, UK.

出版信息

Clin Exp Immunol. 2024 May 16;216(3):293-306. doi: 10.1093/cei/uxae019.

Abstract

Sepsis is characterized by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility of identifying integrative patterns from clinical parameters, plasma biomarkers, and extensive phenotyping of blood immune cells. While no single variable had sufficient predictive power, models that combined five and more features showed a macro area under the curve (AUC) of 0.85 to predict 90-day mortality after sepsis diagnosis, and a macro AUC of 0.86 to discriminate between Gram-positive and Gram-negative bacterial infections. Parameters associated with the cellular immune response contributed the most to models predictive of 90-day mortality, most notably, the proportion of T cells among PBMCs, together with expression of CXCR3 by CD4+ T cells and CD25 by mucosal-associated invariant T (MAIT) cells. Frequencies of Vδ2+ γδ T cells had the most profound impact on the prediction of Gram-negative infections, alongside other T-cell-related variables and total neutrophil count. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical, and clinical parameters.

摘要

脓毒症的特征是宿主对感染的功能失调反应,最终导致危及生命的器官衰竭,需要复杂的患者管理和快速干预。及时诊断脓毒症的根本原因至关重要,确定那些有并发症和死亡风险的患者对于分诊治疗和资源分配至关重要。在这里,我们探讨了可解释的机器学习模型在预测脓毒症患者死亡率和病原体方面的潜力。通过使用一个采用多种特征选择算法的建模管道,我们展示了从临床参数、血浆生物标志物和血液免疫细胞的广泛表型中识别综合模式的可行性。虽然没有单个变量具有足够的预测能力,但结合五个或更多特征的模型显示出预测脓毒症诊断后 90 天死亡率的宏观曲线下面积(AUC)为 0.85,区分革兰氏阳性和革兰氏阴性细菌感染的宏观 AUC 为 0.86。与细胞免疫反应相关的参数对预测 90 天死亡率的模型贡献最大,最显著的是 PBMC 中 T 细胞的比例,以及 CD4+T 细胞上的 CXCR3 和黏膜相关不变 T(MAIT)细胞上的 CD25 的表达。Vδ2+γδ T 细胞的频率对预测革兰氏阴性感染的影响最大,同时还有其他 T 细胞相关变量和总中性粒细胞计数。总的来说,我们的发现强调了在脓毒症患者的血液中测量常规和非常规 T 细胞的比例和激活模式与其他免疫学、生化和临床参数相结合的附加价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb21/11097916/41a916d3ddf0/uxae019_fig8.jpg

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