Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis
Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis
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DOI：
10.1136/jnnp-2012-303768
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发表时间：
2013-04-01
影响因子：
11
通讯作者：
Shaw, Gerry
中科院分区：
文献类型：
--
作者：
Boylan, Kevin B.;Glass, Jonathan D.;Shaw, Gerry
磷酸化神经丝重亚基（pNF-H）是运动轴突的主要结构成分，是肌萎缩侧索硬化（ALS）的一种有前景的假定生物标志物，但主要在CSF中进行研究。我们检查pNF-H浓度在血浆中，血清和CSF作为一个潜在的生物标志物的疾病进展和生存在ALS.Methodology我们测量pNF-H浓度的单克隆夹心ELISA在血浆（n=43），血清和CSF（n=20）ALS患者收集在马约诊所佛罗里达和埃默里大学。我们包括从一个ALS队列（n=20）从早期的试点研究，以评估基线pNF-H水平与疾病进展使用肌萎缩侧索硬化症功能评定量表（ALSFRS-R），生存和解剖区域ALS onset.Results较高的pNF-H水平在血浆中，血清和CSF中的证据表明，与更快的下降ALSFRS-R。有证据表明血清和血浆pNF-H水平较高与生存期较短相关，尽管CSF的证据较弱。pNF-H在血浆中的浓度（n=62）可能是更高的患者与延髓发病比患者与脊髓onset.Conclusions在ALS，血浆中，血清和CSF中的pNF-H浓度增加似乎与更快的疾病进展。影响pNF-H水平或其在血清和血浆中的检测与病程相关的因素可能不同于CSF中的因素。ALS发病部位（延髓与脊髓）可能影响外周血中pNF-H水平的数据似乎值得注意，但需要确认。这些数据支持进一步研究CSF、血清和血浆中的pNF-H作为潜在的ALS生物标志物。
Background The phosphorylated neurofilament heavy subunit (pNF-H), a major structural component of motor axons, is a promising putative biomarker in amyotrophic lateral sclerosis (ALS) but has been studied mainly in CSF. We examined pNF-H concentrations in plasma, serum and CSF as a potential biomarker for disease progression and survival in ALS.Methodology We measured pNF-H concentration by monoclonal sandwich ELISA in plasma (n=43), serum and CSF (n=20) in ALS patients collected at the Mayo Clinic Florida and Emory University. We included plasma from an ALS cohort (n=20) from an earlier pilot study in order to evaluate baseline pNF-H levels in relation to disease progression using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), survival and anatomical region of ALS onset.Results Higher pNF-H levels in plasma, serum and CSF showed evidence of association with faster decline in ALSFRS-R. There was evidence for a relationship of higher serum and plasma pNF-H levels with shorter survival, although evidence was weaker for CSF. pNF-H concentration in plasma (n=62) may be higher in patients with bulbar onset than in patients with spinal onset.Conclusions In ALS, increased pNF-H concentration in plasma, serum and CSF appears to be associated with faster disease progression. Factors affecting pNF-H levels or their detection in serum and plasma in relation to disease course may differ from those in CSF. Data raising the possibility that site of ALS onset (bulbar vs spinal) may influence pNF-H levels in peripheral blood seems noteworthy but requires confirmation. These data support further study of pNF-H in CSF, serum and plasma as a potential ALS biomarker.