Novakova L, Axelsson M, Malmeström C, Zetterberg H, Blennow K, Svenningsson A, Lycke J
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg, Sweden.
Mult Scler Relat Disord. 2020 Nov;46:102463. doi: 10.1016/j.msard.2020.102463. Epub 2020 Aug 22.
Cerebrospinal fluid (CSF) levels of neurofilament light (NFL), a biomarker of axonal damage, and CXCL13, a chemokine involved in B-cell regulation, are both associated with disease activity in multiple sclerosis (MS).
To explore the potential of NFL and CXCL13 to detect residual disease activity in patients with no signs of clinical or ongoing radiological activity and to study the clinical relevance of such activity.
NFL and CXCL13 concentrations were determined with ELISA in CSF obtained from 90 relapsing-remitting (RR) MS and 47 Progressive (Pr) MS (including primary and secondary PrMS) at baseline and after 12 months of follow-up. The patients were assessed at baseline, before initiating or switching disease modifying therapy (DMT) and again after 12 and 27 months of follow-up.
All patients with ongoing disease activity (relapse or contrast-enhancing lesions on MRI) had increased NFL or CXCL13. The proportion of RRMS and PrMS patients without ongoing disease activity with elevation of either NFL or CXCL13 (residual disease activity) was 39% and 50%, respectively, and both were increased in 11% and 16%, respectively. The treatment with DMTs decreased the proportion with residual disease activity in both RRMS and PrMS significantly. We could not show any significant association between residual disease activity and clinical or MRI measures at 12 or 27 months of follow-up.
Although most of this real-world study population had been treated with second-line DMTs and achieved clinical and radiological stability, a significant proportion of patients still displayed increased CSF levels of both NFL and CXCL13, indicating residual disease activity. Thus, these markers seemed considerably more sensitive to disease activity than clinical and MRI measures. However, the long-term clinical significance of such activity remains to be determined.
神经丝轻链（NFL）是轴突损伤的生物标志物，脑脊液（CSF）中NFL水平以及参与B细胞调节的趋化因子CXCL13均与多发性硬化症（MS）的疾病活动相关。
探讨NFL和CXCL13在检测无临床或持续放射学活动迹象患者残留疾病活动方面的潜力，并研究此类活动的临床相关性。
采用酶联免疫吸附测定法（ELISA）测定90例复发缓解型（RR）MS患者和47例进展型（Pr）MS患者（包括原发和继发PrMS）基线及随访12个月后CSF中NFL和CXCL13的浓度。在基线、开始或更换疾病修饰治疗（DMT）前以及随访12个月和27个月后对患者进行评估。
所有有持续疾病活动（复发或MRI上有强化病灶）的患者NFL或CXCL13水平均升高。RRMS和PrMS中无持续疾病活动但NFL或CXCL13升高（残留疾病活动）的患者比例分别为39%和50%，两者均升高的比例分别为11%和16%。DMT治疗显著降低了RRMS和PrMS中残留疾病活动患者的比例。在随访12个月或27个月时，我们未发现残留疾病活动与临床或MRI指标之间存在任何显著关联。
尽管该真实世界研究中的大多数患者已接受二线DMT治疗并实现了临床和放射学稳定，但仍有相当比例的患者CSF中NFL和CXCL13水平升高，表明存在残留疾病活动。因此，这些标志物对疾病活动的敏感性似乎远高于临床和MRI指标。然而，此类活动的长期临床意义仍有待确定。
