Hörauf Jason-Alexander, Schindler Cora Rebecca, Schaible Inna, Wang Minhong, Weber Birte, El Saman André, Pallas Christiane, Widera Marek, Marzi Ingo, Henrich Dirk, Leppik Liudmila
Goethe University Frankfurt, University Hospital, Department of Trauma Surgery and Orthopedics, Frankfurt, Germany.
Goethe University Frankfurt, University Hospital, Institute for Medical Virology, Frankfurt, Germany.
Front Immunol. 2024 Nov 27;15:1478786. doi: 10.3389/fimmu.2024.1478786. eCollection 2024.
Extracellular vesicles (EVs), a heterogeneous group of cell-derived, membrane-enclosed vesicles bearing cell-specific epitopes, have been demonstrated to play a crucial role in neuronal-glial communication and the orchestration of neuroinflammatory processes. However, the existing evidence regarding their function as biomarkers and their role in the pathobiology of traumatic spinal cord injuries (tSCI), particularly in humans, is scarce.
The primary goal of this study was to investigate whether a distinct pattern of EV surface epitopes detected in the plasma of individuals suffering from spinal cord injury is indicative of tSCI.
The study includes patients with isolated tSCI (n=8), polytrauma patients without tSCI (PT; ISS ≥16, n=8), and healthy volunteers (HV; n=8). Plasma samples from tSCI and PT patients were collected right after admission to the emergency room (ER), 24 hours (24h), and 48h after trauma. EVs were isolated via size exclusion chromatography, and EVs' surface epitopes were quantified with MACSPlex EV Kit Neuro (prototype product, Miltenyi Biotec) and compared among the groups. Additionally, results were correlated with clinical parameters.
In total, 19 epitopes differed significantly between the tSCI and the HV groups. Out of these 19, four (CD47, CD56, CD68, and ADAM17) were found to differ significantly among tSCI and PT groups. The expression of the CD47 epitope was found to correlate positively with the American Spinal Injury Association (ASIA) impairment scale.
We identified four potential EV-based tSCI biomarkers (CD47+, CD56+, CD68+, and ADAM17+ EVs) that differ in tSCI, with CD47+ EVs showing a strong correlation with the neurological function in tSCI. Thus, future studies might further specify the relevance of potential tSCI-specific biomarkers and investigate underlying mechanisms of tSCI.
细胞外囊泡（EVs）是一组异质性的、源自细胞的、膜包裹的囊泡，带有细胞特异性表位，已被证明在神经元-胶质细胞通讯和神经炎症过程的协调中起关键作用。然而，关于其作为生物标志物的功能及其在创伤性脊髓损伤（tSCI）病理生物学中的作用，尤其是在人类中的现有证据很少。
本研究的主要目的是调查在脊髓损伤患者血浆中检测到的EV表面表位的独特模式是否指示tSCI。
该研究包括孤立性tSCI患者（n = 8）、无tSCI的多发伤患者（PT；损伤严重度评分≥16，n = 8）和健康志愿者（HV；n = 8）。tSCI和PT患者的血浆样本在急诊室（ER）入院后、创伤后24小时（24h）和48小时采集。通过尺寸排阻色谱法分离EVs，并用MACSPlex EV Kit Neuro（原型产品，美天旎生物技术公司）对EVs的表面表位进行定量，并在各组之间进行比较。此外，结果与临床参数相关。
总共，tSCI组和HV组之间有19个表位存在显著差异。在这19个中，有4个（CD47、CD56、CD68和ADAM17）在tSCI组和PT组之间存在显著差异。发现CD47表位的表达与美国脊髓损伤协会（ASIA）损伤量表呈正相关。
我们鉴定出四种潜在的基于EV的tSCI生物标志物（CD47+、CD56+、CD68+和ADAM17+ EVs），它们在tSCI中存在差异，其中CD47+ EVs与tSCI中的神经功能显示出强相关性。因此，未来的研究可能会进一步明确潜在的tSCI特异性生物标志物的相关性，并研究tSCI的潜在机制。
