JNNP:血浆和脑脊液生物标志物在朊病毒中早期诊断及其与生存关系的比较

2020-09-16 MedSci原创 MedSci原创

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朊病毒病患者的早期诊断和临床管理仍然面临挑战,因为临床表现的变化与其他快速进行性痴呆(RPD)的临床症状存在很大的重叠。而且疾病进展速度和生存时间存在广泛的差距。朊病毒包括自发性,遗传性和获得性(医源性,变异性)。包含克雅氏病,格斯特曼-斯特劳斯勒-舍因克病(GSS),家族性失眠(FI)和易变的蛋白酶敏感性朊病毒病(VPSPr)。克雅氏病是最常见的朊病毒,有不同种亚型。使用脑脊液(CSF)标记的神经损伤,不适应于重复测量,不适合疾病和筛查。因此寻找血液生物标记物是当务之急。

方法:分析了血液和脑脊液样品,博洛尼亚神经科学研究所的神经病理学实验室等负责处理。总共选择了442例病例,其中包括336例朊病毒病例(193例同时有两种生物体可用,125例只有脑脊液可用,18例只有血液可用)和106例快速进行性痴呆病例。此外,分析了37名健康对照者或紧张型头痛患者。EDTA血浆样品按照标准程序收集,等分并保存在-80°C下。我们在SiMOA SR-X分析仪平台(美国马萨诸塞州比勒里卡的Quanterix)上进行了所有血液分析。血浆tau和NfL分别使用SiMOA Human t-tau和SiMOA NF-light优势试剂盒进行测量。 tau的平均测定内和测定间变异系数(CVs)分别为tau为7.1%和11.2%,NfL为3.7%和9.2%。

结果:年龄与血浆神经丝轻链蛋白(NfL)水平相关,而与其他血液和CSF生物标志物无关, 两组患者(所有RPD病例,r = 0.181,p = 0.006)和对照中(r = 0.706,p = 0.003,n = 38)。 性别差异对血液和CSF生物标志物值无影响。 与对照组相比,病毒患者的血浆tau和NfL水平较高(两个比较均p <0.001; NfL年龄校正的线性回归ß= 0.810,p <0.001)。np-RPD患者血浆中的tau和NfL水平高于对照组(tau p = 0.044; NfL p <0.001; NfL年龄调整后的线性回归ß= 0.599,p <0.001)。

血浆生物标志物(tau和NfL)在诊断朊病毒疾病方面不如常规脑脊液标志物。

Abu-Rumeileh SBaiardi SLadogana A, et al Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease

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