From the Department of Surgery, Brigham and Women's Hospital and Harvard Medical School (A.S., B.K.Y., M.G., J.K., J.P.N., W.L., Y.N., T.W., A.S., R.A., J.A.L.); Boston, Massachusetts; Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School (G.A.B. C.H.), Boston, MA.
J Trauma Acute Care Surg. 2019 Aug;87(2):337-341. doi: 10.1097/TA.0000000000002264.
Trauma induces a complex immune response, requiring a systems biology approach to capture multicellular changes. Using mass cytometry by time-of-flight (CyTOF), we evaluated time-dependent changes in peripheral blood in trauma patients to identify changes correlated with infection.
Total leukocytes were prepared via red blood cell lysis using peripheral blood samples from trauma patients with an Injury Severity Score greater than 20 at Days 1, 3, and 5 after injury, and from age- and sex-matched uninjured controls. Cells were stained using a 33-marker immunophenotyping CyTOF panel. Statistics were calculated using one-way analysis of variance with multiple comparisons.
The CyTOF staining demonstrated changes in many cell subsets. The mean expression intensity of CD86 on monocytes decreased significantly at all time points after injury. When the patients were stratified based on development of infection, there was a trend to decreased CD86 expression on monocytes of those patients that developed subsequent infection. Based on stratification, we identified significantly increased expression of CD39 on NK cells only in patients that developed an infection.
This study used a systems biology approach to identify novel changes in circulating immune cell subsets in trauma patients correlating with post-traumatic infection. Decreased expression of CD86, a costimulatory molecule, on monocytes demonstrates that trauma affects the innate system's ability to control T-cell immunity. We also found that CD39 expression on NK cells increased significantly in patients with subsequent infection. CD39 is a protein that generates adenosine, which has immunosuppressive effects on several immune cell types including NK cells. In summary, our results point to pathways that may be central to second-hit infections and further study to delineate these pathways could be key to generating clinical biomarkers or targeted immune therapies for trauma patients.
Prognostic study, level II.
创伤会引发复杂的免疫反应，需要采用系统生物学方法来捕捉细胞的变化。我们使用飞行时间质谱流式细胞术（CyTOF）评估创伤患者外周血中的时间依赖性变化，以确定与感染相关的变化。
使用创伤后损伤严重评分（ISS）大于 20 的创伤患者和年龄、性别匹配的未受伤对照者的外周血样本，通过红细胞裂解法制备全白细胞。使用 33 标志物免疫表型 CyTOF 面板对细胞进行染色。使用单向方差分析和多重比较进行统计计算。
CyTOF 染色显示许多细胞亚群发生了变化。损伤后所有时间点单核细胞上 CD86 的平均表达强度均显著降低。当根据感染的发生对患者进行分层时，发生后续感染的患者单核细胞上 CD86 的表达呈下降趋势。基于分层，我们发现仅在发生感染的患者中 NK 细胞上 CD39 的表达显著增加。
本研究采用系统生物学方法，鉴定出与创伤后感染相关的循环免疫细胞亚群的新型变化。单核细胞上共刺激分子 CD86 的表达降低表明，创伤会影响先天系统控制 T 细胞免疫的能力。我们还发现，随后发生感染的患者 NK 细胞上 CD39 的表达显著增加。CD39 是一种产生腺苷的蛋白，对包括 NK 细胞在内的几种免疫细胞类型具有免疫抑制作用。总之，我们的研究结果表明，这些途径可能是二次打击感染的关键，进一步研究这些途径可能是为创伤患者生成临床生物标志物或靶向免疫治疗的关键。
预后研究，Ⅱ级。
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