Department of Surgery, University of Pittsburgh, Pittsburgh, PA, United States.
Pittsburgh Trauma and Transfusion Medicine Research Center, Division of Trauma and Acute Care Surgery, University of Pittsburgh, Pittsburgh, PA, United States.
Front Immunol. 2022 Nov 30;13:1038086. doi: 10.3389/fimmu.2022.1038086. eCollection 2022.
Severe injury is known to cause a systemic cytokine storm that is associated with adverse outcomes. However, a comprehensive assessment of the time-dependent changes in circulating levels of a broad spectrum of protein immune mediators and soluble immune mediator receptors in severely injured trauma patients remains uncharacterized. To address this knowledge gap, we defined the temporal and outcome-based patterns of 184 known immune mediators and soluble cytokine receptors in the circulation of severely injured patients. Proteomics (aptamer-based assay, SomaLogic, Inc) was performed on plasma samples drawn at 0, 24, and 72 hours (h) from time of admission from 150 trauma patients, a representative subset from the Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock (PAMPer) trial. Patients were categorized into outcome groups including Early Non-Survivors (died within 72 h; ENS; n=38), Non-Resolvers (died after 72 h or required ≥7 days of intensive care; NR; n=78), and Resolvers (survivors that required < 7 days of intensive care; R; n=34), with low Injury Severity Score (ISS) patients from the Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury (STAAMP) trial as controls. The major findings include an extensive release of immune mediators and cytokine receptors at time 0h that is more pronounced in ENS and NR patients. There was a selective subset of mediators elevated at 24 and 72 h to a greater degree in NR patients, including multiple cytokines and chemokines not previously described in trauma patients. These findings were validated in a quantitative fashion using mesoscale discovery immunoassays (MSD) from an external validation cohort (VC) of samples from 58 trauma patients matched for R and NR status. This comprehensive longitudinal description of immune mediator patterns associated with trauma outcomes provides a new level of characterization of the immune response that follows severe injury.
严重损伤会导致全身性细胞因子风暴，与不良预后相关。然而，对于严重创伤患者循环中广泛的蛋白质免疫介质和可溶性免疫介质受体的时间依赖性变化，仍缺乏全面评估。为了弥补这一知识空白，我们定义了严重创伤患者循环中 184 种已知免疫介质和可溶性细胞因子受体的时间和结局依赖性模式。对来自 150 名创伤患者的入院后 0、24 和 72 小时（h）的血浆样本进行了蛋白质组学（基于适体的测定法，SomaLogic，Inc），这是 Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock（PAMPer）试验的一个代表性亚组。患者被分为结局组，包括早期非幸存者（72 小时内死亡；ENS；n=38）、非缓解者（72 小时后死亡或需要≥7 天重症监护；NR；n=78）和缓解者（幸存者需要<7 天重症监护；R；n=34），低损伤严重度评分（ISS）患者来自 Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury（STAAMP）试验作为对照。主要发现包括在 0h 时大量释放免疫介质和细胞因子受体，ENS 和 NR 患者更为明显。在 NR 患者中，有一组选择性的介质在 24 和 72h 时升高到更高的程度，包括之前在创伤患者中未描述的多种细胞因子和趋化因子。这些发现通过来自 58 名创伤患者的外部验证队列（VC）样本的 Mesoscale Discovery Immunoassays（MSD）进行了定量验证，这些患者在 R 和 NR 状态上相匹配。这种与创伤结局相关的免疫介质模式的全面纵向描述提供了对严重损伤后免疫反应的新水平的描述。
