Complex system modeling and engineering for diagnosis, SysDiag - UMR 3145 CNRS/Bio-Rad, 34184 Montpellier Cedex 4, France.
BMC Vet Res. 2010 Nov 2;6:49. doi: 10.1186/1746-6148-6-49.
Transmissible spongiform encephalopathies are fatal neurodegenerative disease occurring in animals and humans for which no ante-mortem diagnostic test in biological fluids is available. In such pathologies, detection of the pathological form of the prion protein (i.e., the causative factor) in blood is difficult and therefore identification of new biomarkers implicated in the pathway of prion infection is relevant.
In this study we used the SELDI-TOF MS technology to analyze a large number of serum samples from control sheep and animals with early phase or late phase scrapie. A few potential low molecular weight biomarkers were selected by statistical methods and, after a training analysis, a protein signature pattern, which discriminates between early phase scrapie samples and control sera was identified.
The combination of early phase biomarkers showed a sensitivity of 87% and specificity of 90% for all studied sheep in the early stage of the disease. One of these potential biomarkers was identified and validated in a SELDI-TOF MS kinetic study of sera from Syrian hamsters infected by scrapie, by western blot analysis and ELISA quantitation.
Differential protein expression profiling allows establishing a TSE diagnostic in scrapie sheep, in the early phase of the disease. Some proteic differences observed in scrapie sheep exist in infected hamsters. Further studies are being performed to identify all the discriminant biomarkers of interest and to test our potential markers in a new cohort of animals.
传染性海绵状脑病是一种在动物和人类中发生的致命神经退行性疾病，目前尚无生物体液中的生前诊断测试。在这种病理学中，在血液中检测到朊病毒蛋白的病理性形式（即致病因子）是困难的，因此鉴定与朊病毒感染途径相关的新生物标志物是相关的。
在这项研究中，我们使用 SELDI-TOF MS 技术分析了大量来自对照绵羊和处于早期或晚期瘙痒病的动物的血清样本。通过统计方法选择了少数潜在的低分子量生物标志物，并在训练分析后，确定了一种能够区分早期瘙痒病样本和对照血清的蛋白质特征模式。
在疾病早期，早期阶段生物标志物的组合对所有研究绵羊的敏感性为 87%，特异性为 90%。这些潜在的生物标志物之一在通过瘙痒病感染的叙利亚仓鼠的 SELDI-TOF MS 动力学研究中通过 Western blot 分析和 ELISA 定量进行了鉴定和验证。
差异蛋白表达谱允许在瘙痒病绵羊的疾病早期建立 TSE 诊断。在瘙痒病绵羊中观察到的一些蛋白质差异存在于感染的仓鼠中。正在进行进一步的研究以鉴定所有有意义的鉴别生物标志物，并在新的动物队列中测试我们的潜在标志物。
