Rübsamen Nicole, Willemse Eline A J, Leppert David, Wiendl Heinz, Nauck Matthias, Karch André, Kuhle Jens, Berger Klaus
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Neurologic Clinic and Policlinic, Departments of Biomedicine and Clinical Research, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Front Neurol. 2022 Jun 14;13:894119. doi: 10.3389/fneur.2022.894119. eCollection 2022.
Neurofilament light (NfL) can be detected in blood of healthy individuals and at elevated levels in those with different neurological diseases. We investigated if the choice of biological matrix can affect results when using NfL as biomarker in epidemiological studies.
We obtained paired serum and EDTA-plasma samples of 299 individuals aged 37-67 years (BiDirect study) and serum samples of 373 individuals aged 65-83 years (MEMO study). In BiDirect, Passing-Bablok analyses were performed to assess proportional and systematic differences between biological matrices. Associations between serum or EDTA-plasma NfL and renal function (serum creatinine, serum cystatin C, glomerular filtration rate, and kidney disease) were investigated using linear or logistic regression, respectively. All regression coefficients were estimated (1) per one ng/L increase and (2) per one standard deviation increase (standardization using z-scores). In MEMO, regression coefficients were estimated (1) per one ng/L increase of serum or calculated EDTA-plasma NfL and (2) per one standard deviation increase providing a comparison to the results from BiDirect.
We found proportional and systematic differences between paired NfL measurements in BiDirect, i.e., serum NfL [ng/L] = -0.33 [ng/L] + 1.11 × EDTA-plasma NfL [ng/L]. Linear regression coefficients for the associations between NfL and renal function did not vary between the different NfL measurements. In MEMO, one standard deviation increase in serum NfL was associated with greater changes in the outcomes than in BiDirect.
Although there are differences between serum and EDTA-plasma NfL, results can be used interchangeably if standardized values are used.
在健康个体的血液中可检测到神经丝轻链（NfL），而在患有不同神经疾病的个体中其水平会升高。我们研究了在流行病学研究中使用NfL作为生物标志物时，生物样本基质的选择是否会影响结果。
我们获取了299名年龄在37 - 67岁个体的配对血清和乙二胺四乙酸（EDTA）血浆样本（BiDirect研究）以及373名年龄在65 - 83岁个体的血清样本（MEMO研究）。在BiDirect研究中，进行了Passing - Bablok分析以评估生物样本基质之间的比例差异和系统差异。分别使用线性回归或逻辑回归研究血清或EDTA血浆NfL与肾功能（血清肌酐、血清胱抑素C、肾小球滤过率和肾脏疾病）之间的关联。所有回归系数的估计分别基于：（1）每增加1 ng/L；（2）每增加一个标准差（使用z分数进行标准化）。在MEMO研究中，回归系数的估计基于：（1）血清或计算得出的EDTA血浆NfL每增加1 ng/L；（2）每增加一个标准差，以便与BiDirect研究的结果进行比较。
我们在BiDirect研究中发现配对的NfL测量值之间存在比例差异和系统差异，即血清NfL[ng/L] = -0.33[ng/L] + 1.11×EDTA血浆NfL[ng/L]。不同NfL测量值之间，NfL与肾功能关联的线性回归系数没有变化。在MEMO研究中，血清NfL增加一个标准差与各项结果的变化相比，比在BiDirect研究中更大。
尽管血清和EDTA血浆NfL之间存在差异，但如果使用标准化值，结果可以互换使用。
