Clinical Neurobiology Unit, Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano 10043, Italy; Department of Neuroscience "Rita Levi Montalcini", University of Turin, Via Cherasco 15, Turin 10100, Italy.
Clinical Neurobiology Unit, Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano 10043, Italy; Department of Neuroscience "Rita Levi Montalcini", University of Turin, Via Cherasco 15, Turin 10100, Italy.
Mult Scler Relat Disord. 2021 Sep;54:103090. doi: 10.1016/j.msard.2021.103090. Epub 2021 Jun 17.
Serum Neurofilament Light (sNFL) is the most promising marker for patient's monitoring in Multiple Sclerosis (MS). However, operating reference values for use in clinical practice are still lacking. Here, we defined sNFL reference cut-off values in a cohort of healthy controls (HC) and assessed their performance in Multiple Sclerosis (MS) patients, as well as the intra-individual sNFL variability.
We measured sNFL by single molecule array (Simoa) assay in 79 HC assessing their correlation with age. Changes of sNFL levels were evaluated during a short-term follow-up (median 67 days between consecutive samples) in a subgroup of 27 participants. sNFL were tested in 23 untreated MS patients, at both diagnostic time and start of therapy (median 80 days after), considering disease activity.
Findings confirmed a correlation between sNFL levels and age in HC, thus cut-off values specific for age decades were calculated. sNFL did not vary significantly with time during short-term follow-up (median CV 13%). sNFL levels in MS patients were higher and demonstrated a higher variability between diagnostic time and treatment start (median CV 39%). According to cut-off values, "pathologic" sNFL levels were found in 57% of MS patients at diagnostic time, and in 30% of samples at treatment start. In particular, "pathologic" sNFL levels were found in 80% of samples (16/20) obtained during a phase of disease activity, while a total of 85% of samples (22/26) associated with inactive disease showed sNFL in the normal range.
This study demonstrates an overall intra-individual stability of sNFL values in the short-term in HC and suggests age-dependent reference cut-off values that could be beneficial for sNFL implementation in clinical practice.
血清神经丝轻链（sNFL）是多发性硬化症（MS）患者监测最有前途的标志物。然而，在临床实践中仍缺乏其使用的参考值。在这里，我们在健康对照组（HC）中定义了 sNFL 的参考截止值，并评估了其在多发性硬化症（MS）患者中的表现，以及个体内 sNFL 的可变性。
我们通过单分子阵列（Simoa）测定法测量了 79 名 HC 中的 sNFL，评估了其与年龄的相关性。在 27 名参与者的亚组中，我们在短期随访期间（两次连续样本之间的中位数为 67 天）评估了 sNFL 水平的变化。我们在 23 名未经治疗的 MS 患者中测试了 sNFL，在诊断时和开始治疗时（中位数为治疗后 80 天）考虑疾病活动。
研究结果证实了 sNFL 水平与 HC 年龄之间的相关性，因此计算了特定年龄的截止值。在短期随访期间，sNFL 随时间变化不大（中位数 CV 为 13%）。MS 患者的 sNFL 水平较高，在诊断时和治疗开始时之间的变异性更高（中位数 CV 为 39%）。根据截止值，在诊断时，57%的 MS 患者的 sNFL 水平“异常”，在治疗开始时，30%的样本 sNFL 水平“异常”。特别是，在疾病活动期间获得的 20 个样本中的 16 个（80%）存在“异常”sNFL 水平，而与无活动疾病相关的 26 个样本中的 22 个（85%）sNFL 水平在正常范围内。
本研究表明，HC 短期个体内 sNFL 值总体稳定，并提示了年龄依赖性的参考截止值，这可能有助于 sNFL 在临床实践中的应用。
