Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany.
Front Immunol. 2024 Mar 12;15:1347767. doi: 10.3389/fimmu.2024.1347767. eCollection 2024.
The goal of this study was to identify changes in extracellular vesicles (EV) surface proteins specific to traumatic brain injury (TBI), which could be used as a diagnostic and prognostic tool in polytrauma patients.
Known serum TBI-specific biomarkers (S100B, NSE, and GFAP), which can predict the severity and outcome of isolated TBI, lose their predictive value in the presence of additional extracranial injuries. Extracellular vesicles (EVs) are released from cells in response to various stimuli and carry specific cargo/surface molecules that could be used for tracking injury-responding cells.
EVs were isolated using size exclusion chromatography (SEC) from the plasma of two groups of patients (with isolated TBI, ISS≥16, AIShead≥4, n=10; and polytraumatized patients without TBI ISS≥16, AIShead=0, n=10) collected in the emergency room and 48 h after trauma. EVs' surface epitope expression was investigated using a neurospecific multiplex flow cytometry assay and compared with healthy controls (n=10). Three enrichments of EV epitopes found to be specific to TBI were validated by western blot.
The expression of 10 EV epitopes differed significantly among the patient and control groups, and five of these epitopes (CD13, CD196, MOG, CD133, and MBP) were TBI-specific. The increased expression of CD196, CD13, and MOG-positive EVs was validated by western blot.
Our data showed that TBI is characterized by a significant increase of CD13, CD196, MOG, CD133, and MBP-positive EVs in patients' plasma. A high level of MOG-positive EVs negatively correlated with the Glasgow Coma Scale score at admission and could be an indicator of poor neurological status.
本研究旨在鉴定创伤性脑损伤（TBI）特有的细胞外囊泡（EV）表面蛋白变化，以期将其作为多发伤患者的一种诊断和预后工具。
已知的血清 TBI 特异性生物标志物（S100B、NSE 和 GFAP）可预测单纯 TBI 的严重程度和结局，但在存在额外的颅外损伤时，其预测价值丧失。细胞外囊泡（EVs）是细胞在受到各种刺激时释放的，携带特定的货物/表面分子，可用于追踪损伤反应细胞。
采用尺寸排阻色谱（SEC）从两组患者（单纯 TBI，ISS≥16，AIShead≥4，n=10；多发伤患者无 TBI，ISS≥16，AIShead=0，n=10）的血浆中分离 EVs，并在创伤后 48 h 收集。采用神经特异性多重流式细胞术检测 EV 表面表位表达，并与健康对照组（n=10）进行比较。通过 Western blot 验证了三个被鉴定为 TBI 特异性的 EV 表位富集。
患者组和对照组之间 10 个 EV 表位的表达差异有统计学意义，其中 5 个表位（CD13、CD196、MOG、CD133 和 MBP）为 TBI 特异性。Western blot 验证了 CD196、CD13 和 MOG 阳性 EVs 的表达增加。
我们的数据表明，TBI 患者血浆中 CD13、CD196、MOG、CD133 和 MBP 阳性 EVs 的表达显著增加。MOG 阳性 EVs 水平高与入院时的格拉斯哥昏迷评分呈负相关，可能是神经功能状态不良的指标。
