Novakova Lenka, Axelsson Markus, Khademi Mohsen, Zetterberg Henrik, Blennow Kaj, Malmeström Clas, Piehl Fredrik, Olsson Tomas, Lycke Jan
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Neurochem. 2017 Apr;141(2):296-304. doi: 10.1111/jnc.13881. Epub 2016 Nov 29.
Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes. We included 59 RRMS patients and 39 healthy controls. The concentrations of C-X-C motif chemokine 13 (CXCL13), C-C motif chemokine ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein, neurofilament light protein (NFL), and neurogranin were determined by ELISA, and chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RRMS patients had higher levels of NFL, CXCL13, CHI3L1, and CHIT1 than controls (p < 0.001). Subgroup analysis revealed higher NFL, CXCL13 and CHIT1 levels in patients treated with first-line therapy compared to second-line therapy (p = 0.008, p = 0.001 and p = 0.026, respectively). NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new magnetic resonance imaging lesions. Furthermore, we found an association between inflammatory and degenerative biomarkers. The results indicate that CSF levels of NFL, CXCL13, CHI3L1, and CHIT1 correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy.
脑脊液（CSF）生物标志物可以反映复发缓解型多发性硬化症（RRMS）病理生理学的不同方面。了解不同疾病修正疗法对CSF生物标志物谱的影响，可能会增加它们在临床实践中的应用以及监测治疗效果的适用性。本研究调查了一线（干扰素β）和二线（那他珠单抗）疗法对RRMS患者七种CSF生物标志物的影响及其与临床和影像学结果的相关性。我们纳入了59例RRMS患者和39名健康对照。采用酶联免疫吸附测定法（ELISA）测定C-X-C基序趋化因子13（CXCL13）、C-C基序趋化因子配体2（CCL2）、几丁质酶-3样蛋白1（CHI3L1）、胶质纤维酸性蛋白、神经丝轻链蛋白（NFL）和神经颗粒素的浓度，采用荧光分光光度法分析壳三糖苷酶（CHIT1）。RRMS患者的NFL、CXCL13、CHI3L1和CHIT1水平高于对照组（p < 0.001）。亚组分析显示，与二线治疗相比，接受一线治疗的患者NFL、CXCL13和CHIT1水平更高（分别为p = 0.008、p = 0.001和p = 0.026）。NFL和CHIT1水平与复发状态相关，NFL和CXCL13水平与新的磁共振成像病变形成相关。此外，我们发现炎症和退行性生物标志物之间存在关联。结果表明，NFL、CXCL13、CHI3L1和CHIT1的CSF水平与临床和/或影像学疾病活动相关，为评估治疗效果提供了额外的维度。
