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评估多发性硬化症患者脑脊液中神经元退行性变和神经炎症的生物标志物-骨桥蛋白作为临床严重程度的潜在标志物。

Evaluating biomarkers of neuronal degeneration and neuroinflammation in CSF of patients with multiple sclerosis-osteopontin as a potential marker of clinical severity.

机构信息

Department of Neurology, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary.

出版信息

J Neurol Sci. 2013 Aug 15;331(1-2):38-42. doi: 10.1016/j.jns.2013.04.024. Epub 2013 May 21.

Abstract

Biomarkers capable of predicting the clinical course and the rate of disease progression in multiple sclerosis are currently unavailable. Our objective was to examine if the levels of proteins associated with axonal and neuronal degeneration (Tau, p-Tau and β-amyloid(1-42)) and T-cell-mediated autoimmunity (osteopontin) are altered in the cerebrospinal fluid (CSF) of MS patients, and to assess their potential in reflecting the clinical severity and predicting the progression and clinical evolution of early MS. The CSF samples collected from patients presenting with different clinical forms of MS were evaluated by enzyme-linked immunosorbent assays. The patients were regularly followed-up and their clinical status was re-evaluated 5 years after sampling. The results demonstrated that while CSF levels of Tau, p-Tau and β-amyloid(1-42) did not differ between MS and Control groups, the levels of osteopontin were significantly elevated in MS patients. This increase was associated with the presence of a relapse and correlated with clinical severity, which findings were independent of age and blood-CSF barrier function. However, none of the examined protein levels differed significantly between groups with different clinical evolutions and no positive correlations with clinical progression could be detected. We conclude that Tau, p-Tau and β-amyloid(1-42) are inappropriate as biomarkers in MS. This is the first report on CSF osteopontin as an independent marker of clinical severity in definite MS.

摘要

目前尚无能够预测多发性硬化症临床病程和疾病进展速度的生物标志物。我们的目的是检测与轴突和神经元变性(Tau、p-Tau 和 β-淀粉样蛋白(1-42))和 T 细胞介导的自身免疫(骨桥蛋白)相关的蛋白质在多发性硬化症患者脑脊液(CSF)中的水平是否发生改变,并评估其在反映临床严重程度以及预测早期多发性硬化症进展和临床演变方面的潜在价值。通过酶联免疫吸附测定法评估了来自具有不同临床形式多发性硬化症患者的 CSF 样本。对患者进行了定期随访,并在采样后 5 年重新评估其临床状况。结果表明,尽管 Tau、p-Tau 和 β-淀粉样蛋白(1-42)在多发性硬化症患者和对照组之间的 CSF 水平没有差异,但骨桥蛋白的水平在多发性硬化症患者中显著升高。这种增加与复发的发生有关,并与临床严重程度相关,这些发现独立于年龄和血脑屏障功能。然而,在不同临床演变的组之间,所检查的蛋白质水平没有显著差异,也没有检测到与临床进展的正相关关系。我们得出结论,Tau、p-Tau 和 β-淀粉样蛋白(1-42)不适合作为多发性硬化症的生物标志物。这是 CSF 骨桥蛋白作为明确多发性硬化症临床严重程度的独立标志物的首次报道。

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