Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
Genomics and Bioinformatics of Infectious Diseases, Institute for Animal Genomics, University of Veterinary Medicine Hannover, Hannover, Germany.
Front Immunol. 2024 Jan 12;14:1310271. doi: 10.3389/fimmu.2023.1310271. eCollection 2023.
The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients.
Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective.
In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation.
By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis.
Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.
本研究旨在确定一组生物标志物，以区分早期脓毒症患者和非感染性创伤患者。
由于其共同的症状，尽管临床意义不同，即不同的治疗方法，准确地区分创伤引起的无菌性炎症和真正的感染性脓毒症是一个复杂的危及生命的医学挑战。因此，及时准确地识别创伤患者中的脓毒症对于确保及时和针对性的医疗干预至关重要，这些干预措施可以最终导致改善治疗管理和患者预后。在没有脓毒症的创伤患者中适当避免使用抗生素在患者和环境方面也很重要。
在这项概念验证研究中，我们采用了先进的技术，包括基质辅助激光解吸/电离（MALDI）和多重抗体阵列（MAA），以确定一组区分实际脓毒症和创伤引起的无菌性炎症的生物标志物。
通过比较不同时间点的患者组（对照组、感染和非感染性创伤以及机械通气的感染性休克患者），我们发现了与早期创伤引起的无菌性炎症和脓毒症相关的不同蛋白质模式。SYT13 和 IL1F10 作为潜在的早期脓毒症生物标志物出现，而 A2M 的水平降低表明创伤引起的炎症和脓毒症情况。此外，在创伤患者中，TREM1 的水平在后期更高。此外，富集分析显示，创伤引起的炎症和脓毒症之间的炎症反应存在差异，与补体和凝血级联相关的蛋白质升高，而与局灶粘连相关的蛋白质减少。
因此，我们的发现表明，需要结合生物标志物来开发新的诊断方法，以区分创伤引起的无菌性炎症和实际的感染性脓毒症。
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