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多发性硬化症的蛋白质生物标志物:不同形式多发性硬化症脑脊液候选蛋白生物标志物的半定量分析。

Protein biomarkers for multiple sclerosis: semi-quantitative analysis of cerebrospinal fluid candidate protein biomarkers in different forms of multiple sclerosis.

机构信息

Dr Orhan Öcalgiray Molecular Biology-Biotechnology and Genetics Research Centre, Istanbul Technical University, Turkey.

出版信息

Mult Scler. 2012 Aug;18(8):1081-91. doi: 10.1177/1352458511433303. Epub 2012 Jan 17.

Abstract

BACKGROUND

The complex pathogenesis of multiple sclerosis, combined with an unpredictable prognosis, requires identification of disease-specific diagnostic and prognostic biomarkers.

OBJECTIVE

To determine whether inflammatory proteins, such as neurofilament light chain, myelin oligodendrocyte glycoprotein and myelin basic protein, and neurodegenerative proteins, such as tau and glial fibrillary acidic protein, can serve as biomarkers for predicting the clinical subtype and prognosis of MS.

METHODS

Cerebrospinal fluid and serum samples were collected from patients with a diagnosis of clinically isolated syndrome (n = 46), relapsing-remitting MS (n = 67) or primary-progressive MS (n = 22) along with controls having other non-inflammatory neurological disease (n = 22). Western blot analyses were performed for the listed proteins. Protein levels were compared among different clinical subtypes using one-way analysis of variance analysis. The k-nearest neighbour algorithm was further used to assess the predictive use of these proteins for clinical subtype classification.

RESULTS

The results showed that each of tau, GFAP, MOG and NFL protein concentrations differed significantly (p < 0.001) in multiple sclerosis clinical subtypes compared with the controls. Levels of the proteins also differed between the multiple sclerosis clinical subtypes, which may be associated with the underlying disease process. Classification studies revealed that these proteins might be useful for identifying multiple sclerosis clinical subtypes.

CONCLUSIONS

We showed that select biomarkers may have potential in identifying multiple sclerosis clinical subtypes. We also showed that the predictive value of the prognosis increased when using a combination of the proteins versus using them individually.

摘要

背景

多发性硬化症的发病机制复杂,预后不可预测,因此需要确定特定于疾病的诊断和预后生物标志物。

目的

确定神经丝轻链、髓鞘少突胶质细胞糖蛋白和髓鞘碱性蛋白等炎症蛋白和tau 和神经胶质纤维酸性蛋白等神经退行性蛋白是否可以作为预测多发性硬化症临床亚型和预后的生物标志物。

方法

收集了临床孤立综合征(n = 46)、复发缓解型多发性硬化症(n = 67)和原发性进展型多发性硬化症(n = 22)患者以及患有其他非炎症性神经系统疾病的对照者(n = 22)的脑脊液和血清样本。对列出的蛋白进行了 Western blot 分析。使用单因素方差分析比较了不同临床亚型之间的蛋白水平。进一步使用 k-最近邻算法评估这些蛋白对临床亚型分类的预测用途。

结果

结果表明,tau、GFAP、MOG 和 NFL 蛋白浓度在多发性硬化症临床亚型与对照组之间差异均有统计学意义(p < 0.001)。这些蛋白在多发性硬化症的临床亚型之间也存在差异,这可能与潜在的疾病过程有关。分类研究表明,这些蛋白可能有助于识别多发性硬化症的临床亚型。

结论

我们表明,一些生物标志物可能有助于识别多发性硬化症的临床亚型。我们还表明,当使用这些蛋白的组合而非单独使用时,预测预后的价值会增加。

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