解密炎症性疾病中的蛋白质组表达:质谱分析比较人类脑脊液中的感染性、非感染性和创伤性脑损伤。

IF 1.8 Q3 CLINICAL NEUROLOGY
Neurotrauma reports Pub Date : 2024-09-20 eCollection Date: 2024-01-01 DOI:10.1089/neur.2024.0050
Philip Dyhrfort, Caroline Lindblad, Anna Widgren, Johan Virhammar, Fredrik Piehl, Jonas Bergquist, Faiez Al Nimer, Elham Rostami
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引用次数: 0

摘要

中枢神经系统(CNS)对损伤会产生复杂的炎症反应。影响大脑的创伤性、感染性和非感染性疾病都会引起炎症级联反应。中枢神经系统的炎症反应包括促炎和抗炎反应,其中既有众所周知的蛋白质,也有许多在这些过程中鲜为人知的蛋白质。本研究的目的是利用质谱分析法,探讨创伤性脑损伤(TBI)与其他中枢神经系统损伤相比所具有的独特炎症反应。共有 56 名患者的脑脊液(CSF)通过质谱仪进行了分析。其中,21 名急性创伤性脑损伤患者的脑脊液是通过脑室外引流管(EVD)收集的。然后,将所得蛋白质结果与 14 名非感染性中枢神经系统疾病(包括复发性多发性硬化症、抗 N-甲基-d-天冬氨酸受体脑炎、急性播散性脑脊髓炎)患者腰椎穿刺采集的 CSF 以及 14 名进行性多灶性白质脑病、单纯疱疹性脑炎和其他类型病毒性脑膜炎患者的 CSF 进行比较。我们还利用了 n = 7 个健康对照组(HCs)。在对创伤性脑损伤和非感染性炎症性中枢神经系统疾病的比较中,55 种蛋白质的浓度在组间存在显著差异。其中,创伤性脑损伤组分别有 23 和 32 个蛋白质上调和下调。两组中均未发现独特的蛋白质。在 TBI 和 HC 的比较中,有 51 种蛋白质存在显著差异,其中 TBI 组分别有 24 和 27 种蛋白质上调和下调。两种蛋白质(纤维蛋白原 gamma 链和转酮酶)在 TBI 组的所有样本中都得到了唯一鉴定。在最后一项比较中,即创伤性脑损伤与感染性中枢神经系统炎症性疾病的比较中,两组之间有 51 个蛋白质存在差异,创伤性脑损伤组分别有 19 个和 32 个蛋白质被上调和下调,没有发现独特的蛋白质。由于两组之间的差异较大,因此在差异调控的蛋白质中选择了以下蛋白质进行进一步的深入分析:APOE、CFB、CHGA、CHI3L1、C3、FCGBP、FGA、GSN、IGFBP7、LRG1、SERPINA3、SOD3 和 TTR。我们在 TBI 患者的 CSF 中发现了与 HC 和不同疾病对照组相比截然不同的蛋白质组特征,这表明炎症因子、代谢反应和细胞完整性之间存在特定的相互作用。与主要的感染性或炎症性疾病相比,独特的炎症通路似乎参与其中,并有可能成为未来的治疗目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid.

The central nervous system (CNS) evokes a complex inflammatory response to injury. Inflammatory cascades are present in traumatic, infectious, and noninfectious disorders affecting the brain. It contains a mixture of pro- and anti-inflammatory reactions involving well-known proteins, but also numerous proteins less explored in these processes. The aim of this study was to explore the distinct inflammatory response in traumatic brain injury (TBI) compared with other CNS injuries by utilization of mass-spectrometry. In total, 56 patients had their cerebrospinal fluid (CSF) analyzed with the use of mass-spectrometry. Among these, CSF was collected via an external ventricular drain (EVD) from n = 21 patients with acute TBI. The resulting protein findings were then compared with CSF obtained by lumbar puncture from n = 14 patients with noninfectious CNS disorders comprising relapsing-remitting multiple sclerosis, anti-N-methyl-d-aspartate-receptor encephalitis, acute disseminated encephalomyelitis, and n = 14 patients with progressive multifocal leukoencephalopathy, herpes simplex encephalitis, and other types of viral meningitis. We also utilized n = 7 healthy controls (HCs). In the comparison between TBI and noninfectious inflammatory CNS disorders, concentrations of 55 proteins significantly differed between the groups. Among them, 23 and 32 proteins were up- and downregulated, respectively, in the TBI group. No proteins were uniquely identified in either group. In the comparison of TBI and HC, 51 proteins were significantly different, with 24 and 27 proteins being up- and downregulated, respectively, in TBI. Two proteins (fibrinogen gamma chain and transketolase) were uniquely identified in all samples of the TBI group. Also in the last comparison, TBI versus infectious inflammatory CNS disorders, 51 proteins differed between the two groups, with 19 and 32 proteins being up- and downregulated, respectively, in TBI, and no unique proteins being identified. Due to large discrepancies between the groups compared, the following proteins were selected for further deeper analysis among those being differentially regulated: APOE, CFB, CHGA, CHI3L1, C3, FCGBP, FGA, GSN, IGFBP7, LRG1, SERPINA3, SOD3, and TTR. We found distinct proteomic profiles in the CSF of TBI patients compared with HC and different disease controls, indicating a specific interplay between inflammatory factors, metabolic response, and cell integrity. In relation to primarily infectious or inflammatory disorders, unique inflammatory pathways seem to be engaged, and could potentially serve as future treatment targets.

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CiteScore
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