Verberk Inge M W, Koel-Simmelink Marleen, Twaalfhoven Harry, Vrenken Hugo, Korth Carsten, Killestein Joep, Teunissen Charlotte E, Bridel Claire
Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Mult Scler Relat Disord. 2021 May;50:102840. doi: 10.1016/j.msard.2021.102840. Epub 2021 Feb 10.
Neurofilament heavy (NfH) is a promising biomarker for neuro-axonal damage in Multiple Sclerosis (MS). We compared the performance of high-sensitivity serum-NfH immunoassays, with as aim to investigate the value of serum-NfH as biomarker for MS.
We measured serum-NfH in 76 MS patients with Simoa (one commercial, one in-house) or Luminex assays. Serum-NfH measured by the immunoassay with greatest sensitivity was related to clinical and radiological outcomes with age and sex-adjusted linear regression analysis, and to biological outcomes cerebrospinal fluid (CSF)-NfH, serum neurofilament light (NfL) and CSF-NfL with Spearman's correlation analysis.
With the commercial Simoa assay, we obtained 100% serum-NfH detectability (in-house Simoa: 70%, Luminex: 61%), with lowest coefficient of variation (CV) between duplicates of 11%CV (in-house Simoa: 22%CV, Luminex: 30%CV). Serum-NfH quantified with the commercial Simoa assay was associated with disease duration (standardized beta (sβ) = 0.28, p = 0.034), T2 lesion volume (sβ = 0.23, p = 0.041), and tended to associate with black hole count (sβ = 0.21, p = 0.084) but not with Expanded Disease Disability Score (EDSS) or normalized brain volume (all: p>0.10). Furthermore, serum-NfH showed correlations with CSF-NfH (rho = 0.27, p = 0.018) and serum-NfL (rho=0.44, p < 0.001), but not with CSF-NfL.
Serum-NfH can be quantified with high-sensitivity technology. Cross-sectionally, we observed some weak correlations of serum-NfH with MS disease burden parameters, suggesting there might be some utility for serum-NfH as biomarker for MS disease burden.
神经丝重链（NfH）是多发性硬化症（MS）神经轴突损伤的一种很有前景的生物标志物。我们比较了高灵敏度血清NfH免疫测定法的性能，旨在研究血清NfH作为MS生物标志物的价值。
我们使用Simoa（一种商业方法、一种内部方法）或Luminex测定法测量了76例MS患者的血清NfH。通过灵敏度最高的免疫测定法测得的血清NfH，经年龄和性别调整的线性回归分析与临床和放射学结果相关，并经Spearman相关性分析与生物学结果脑脊液（CSF）-NfH、血清神经丝轻链（NfL）和CSF-NfL相关。
使用商业Simoa测定法，我们获得了100%的血清NfH可检测性（内部Simoa：70%，Luminex：61%），重复检测间的变异系数（CV）最低为11%CV（内部Simoa：22%CV，Luminex：30%CV）。用商业Simoa测定法定量的血清NfH与疾病持续时间相关（标准化β（sβ）=0.28，p=0.034）、T2病变体积相关（sβ=0.23，p=0.041），并且倾向于与黑洞计数相关（sβ=0.21，p=0.084），但与扩展残疾状态量表（EDSS）或正常脑体积无关（所有p>0.10）。此外，血清NfH与CSF-NfH相关（rho=0.27，p=0.018）和血清NfL相关（rho=0.44，p<0.001），但与CSF-NfL无关。
血清NfH可用高灵敏度技术进行定量。横断面研究中，我们观察到血清NfH与MS疾病负担参数存在一些弱相关性，提示血清NfH作为MS疾病负担生物标志物可能有一定用途。
