对全血进行深度免疫分析，以确定与大创伤后患者预后相关的早期免疫特征。
Deep immune profiling of whole blood to identify early immune signatures that correlate to patient outcome after major trauma.
机构信息
From the Division of Trauma, Emergency Surgery & Surgical Critical Care, Department of Surgery (A.E.M., M.E.H., L.N., C.N., S.M., I.v.E., G.C.V.), and Vaccine and Immunotherapy Center, Division of Infectious Diseases, Department of Medicine (S.R.P., J.H., M.P., P.R.), Massachusetts General Hospital, Boston, Massachusetts.
出版信息
J Trauma Acute Care Surg. 2021 Jun 1;90(6):959-966. doi: 10.1097/TA.0000000000003170.
BACKGROUND
Major injury results in an early cascade of immunologic responses that increase susceptibility to infection and multiorgan dysfunction. Detailed immune profiling by mass cytometry has the potential to identify immune signatures that correspond to patient outcomes. Our objective was to determine the prognostic value of immune signatures early after major trauma injury.
METHODS
Trauma patients (n = 17) were prospectively enrolled between September 2018 and December 2019. Serial whole blood samples were obtained from trauma patients (mean Injury Severity Score, 26.2; standard error of the mean, 3.7) at Days 1 and 3 after injury, and from age- and sex-matched uninjured controls using a standardized protocol for fixation, storage, and labeling. Computational analyses including K-nearest neighbor automated clustering of immune cells and Spearman's correlation analysis were used to identify correlations between cell populations, clinical measures, and patient outcomes.
RESULTS
Analysis revealed nine immune cell clusters that correlated with one or more clinical outcomes. On Days 1 and 3 postinjury, the abundance of immature neutrophil and classical monocytes exhibited a strong positive correlation with increased intensive care unit and hospital length of stay. Conversely, the abundance of CD4 T-cell subsets, namely Th17 cells, is associated with improved patient outcomes including decreased ventilator days (r = -0.76), hospital-acquired pneumonia (r = -0.69), and acute kidney injury (r = -0.73).
CONCLUSION
Here, we provide a comprehensive multitime point immunophenotyping analysis of whole blood from patients soon after traumatic injury to determine immune correlates of adverse outcomes. Our findings indicate that alterations in myeloid-origin cell types may contribute to immune dysfunction after injury. Conversely, the presence of effector T cell populations corresponds with decreased hospital length of stay and organ dysfunction. Overall, these data identify novel immune signatures following traumatic injury that support the view that monitoring of immune (sub)-populations may provide clinical decision-making support for at-risk patients early in their hospital course.
LEVEL OF EVIDENCE
Prognostic/Epidemiologic, Level IV.
背景
严重损伤会导致早期免疫反应级联增加，从而增加感染和多器官功能障碍的易感性。通过质谱细胞术进行详细的免疫分析有可能确定与患者预后相关的免疫特征。我们的目的是确定严重创伤后早期免疫特征的预后价值。
方法
2018 年 9 月至 2019 年 12 月，前瞻性纳入创伤患者（n=17）。使用标准化方案对创伤患者（平均损伤严重程度评分 26.2，均数标准差 3.7）在损伤后第 1 天和第 3 天以及年龄和性别匹配的未受伤对照者进行连续全血样本采集，包括固定、储存和标记。采用 K-最近邻自动聚类免疫细胞和 Spearman 相关性分析等计算分析方法，确定细胞群与临床指标和患者预后之间的相关性。
结果
分析显示 9 个免疫细胞簇与一个或多个临床结局相关。在损伤后第 1 天和第 3 天，幼稚中性粒细胞和经典单核细胞的丰度与重症监护病房和住院时间的延长呈强正相关。相反，CD4 T 细胞亚群（即 Th17 细胞）的丰度与患者预后改善相关，包括减少通气天数（r=-0.76）、医院获得性肺炎（r=-0.69）和急性肾损伤（r=-0.73）。
结论
在这里，我们对创伤后不久的患者全血进行了全面的多时间点免疫表型分析，以确定不良结局的免疫相关因素。我们的研究结果表明，髓系细胞类型的改变可能导致损伤后免疫功能障碍。相反，效应 T 细胞群的存在与住院时间和器官功能障碍减少相关。总的来说，这些数据确定了创伤后新的免疫特征，支持了这样一种观点，即监测免疫（亚）群可能为高危患者在住院期间早期提供临床决策支持。
证据水平
预后/流行病学，IV 级。
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