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脊髓灰质炎后遗症新型候选蛋白质生物标志物的鉴定——对诊断、神经退行性变和神经炎症的意义

Identification of novel candidate protein biomarkers for the post-polio syndrome - implications for diagnosis, neurodegeneration and neuroinflammation.

作者信息

Gonzalez Henrik, Ottervald Jan, Nilsson Kerstin C, Sjögren Niclas, Miliotis Tasso, Von Bahr Helena, Khademi Mohsen, Eriksson Bodil, Kjellström Sven, Vegvari Akos, Harris Robert, Marko-Varga György, Borg Kristian, Nilsson Johan, Laurell Thomas, Olsson Tomas, Franzén Bo

机构信息

Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.

出版信息

J Proteomics. 2009 Jan 30;71(6):670-81. doi: 10.1016/j.jprot.2008.11.014. Epub 2008 Dec 3.

Abstract

Survivors of poliomyelitis often develop increased or new symptoms decades after the acute infection, a condition known as post-polio syndrome (PPS). The condition affects 20-60% of previous polio patients, making it one of the most common causes of neurological deficits worldwide. The underlying pathogenesis is not fully understood and accurate diagnosis is not feasible. Herein we investigated whether it was possible to identify proteomic profile aberrations in the cerebrospinal fluid (CSF) of PPS patients. CSF from 15 patients with well-defined PPS were analyzed for protein expression profiles. The results were compared to data obtained from nine healthy controls and 34 patients with other non-inflammatory diseases which served as negative controls. In addition, 17 samples from persons with secondary progressive multiple sclerosis (SPMS) were added as relevant age-matched references for the PPS samples. The CSF of persons with PPS displayed a disease-specific and highly predictive (p=0.0017) differential expression of five distinct proteins: gelsolin, hemopexin, peptidylglycine alpha-amidating monooxygenase, glutathione synthetase and kallikrein 6, respectively, in comparison with the control groups. An independent ELISA confirmed the increase of kallikrein 6. We suggest that these five proteins should be further evaluated as candidate biomarkers for the diagnosis and development of new therapies for PPS patients.

摘要

小儿麻痹症幸存者常在急性感染数十年后出现症状加重或出现新症状,这种情况被称为小儿麻痹后遗症(PPS)。该病症影响20%至60%的既往小儿麻痹症患者,使其成为全球神经功能缺损最常见的病因之一。其潜在发病机制尚未完全明确,准确诊断也不可行。在此,我们研究了是否有可能识别小儿麻痹后遗症患者脑脊液(CSF)中的蛋白质组学特征异常。对15例明确诊断为小儿麻痹后遗症的患者的脑脊液进行蛋白质表达谱分析。将结果与9名健康对照者以及34例患有其他非炎症性疾病的患者(作为阴性对照)的数据进行比较。此外,还添加了17例继发进展型多发性硬化症(SPMS)患者的样本作为与小儿麻痹后遗症样本年龄匹配的相关参考。与对照组相比,小儿麻痹后遗症患者的脑脊液显示出五种不同蛋白质(分别为凝溶胶蛋白、血红素结合蛋白、肽基甘氨酸α-酰胺化单加氧酶、谷胱甘肽合成酶和激肽释放酶6)具有疾病特异性且高度预测性(p = 0.0017)的差异表达。一项独立的酶联免疫吸附测定(ELISA)证实了激肽释放酶6的增加。我们建议,这五种蛋白质应作为小儿麻痹后遗症患者诊断和新疗法开发的候选生物标志物进行进一步评估。

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