The immune response of critically ill patients, such as those with sepsis, severe trauma, or major surgery, is heterogeneous and dynamic, but its characterization and impact on outcomes are poorly understood. Until now, the primary challenge in advancing our understanding of the disease has been to concurrently address both multiparametric and temporal aspects. We used a clustering method to identify distinct groups of patients, based on various immune marker trajectories during the first week after admission to ICU. In 339 severely injured patients, we initially longitudinally clustered common biomarkers (both soluble and cellular parameters), whose variations are well-established during the immunosuppressive phase of sepsis. We then applied this multi-trajectory clustering using markers composed of whole blood immune-related mRNA. We found that both sets of markers revealed two immunotypes, one of which was associated with worse outcomes, such as increased risk of hospital-acquired infection and mortality, and prolonged hospital stays. This immunotype showed signs of both hyperinflammation and immunosuppression, which persisted over time. Our study suggest that the immune system of critically ill patients can be characterized by two distinct longitudinal immunotypes, one of which included patients with a persistently dysregulated and impaired immune response. This work confirms the relevance of such methodology to stratify patients and pave the way for further studies using markers indicative of potential immunomodulatory drug targets.

中文翻译：

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多个免疫标记轨迹的整合聚类揭示了严重受伤患者的不同免疫类型


重症患者（例如脓毒症、严重创伤或重大手术患者）的免疫反应是异质且动态的，但其特征及其对结果的影响却知之甚少。到目前为止，推进我们对该疾病的理解的主要挑战是同时解决多参数和时间方面的问题。我们根据入住 ICU 后第一周内的各种免疫标记物轨迹，使用聚类方法来识别不同的患者组。在 339 名严重受伤的患者中，我们最初对常见的生物标志物（可溶性参数和细胞参数）进行纵向聚类，这些生物标志物的变化在脓毒症的免疫抑制阶段已经确定。然后，我们使用由全血免疫相关 mRNA 组成的标记来应用这种多轨迹聚类。我们发现两组标记物都显示出两种免疫类型，其中一种与更糟糕的结果相关，例如医院获得性感染和死亡率风险增加以及住院时间延长。这种免疫型显示出过度炎症和免疫抑制的迹象，并且随着时间的推移持续存在。我们的研究表明，危重患者的免疫系统可以以两种不同的纵向免疫类型为特征，其中一种包括免疫反应持续失调和受损的患者。这项工作证实了这种方法对患者进行分层的相关性，并为使用指示潜在免疫调节药物靶点的标记物进行进一步研究铺平了道路。