Institute of Neurology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy.
Institute of General Pathology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Italy.
Mult Scler Relat Disord. 2019 Oct;35:176-181. doi: 10.1016/j.msard.2019.07.030. Epub 2019 Jul 28.
Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, neurodegenerative disorder. Many studies are investigating the potential role of body fluid biomarkers as prognostic factors for early identification of patients presenting with clinical isolated syndrome (CIS) at high risk for conversion to MS or to recognize RRMS patients at high risk for progression.
To evaluate the correlation between levels of BAFF, chitinase 3-like 1 (CHI3L1), sCD163, Osteopontin (OPN), both on serum and cerebral spinal fluid (CSF), and the disease activity and progression. We also want to explore a possible relationship between serological and CSF biomarker's levels.
We enrolled 82 patients between June 2014 and June 2016. Seventy-one received a diagnosis of demyelinating disease of CNS (46 RRMS and 25 CIS), while 11 were affected by other neurological diseases. All patients underwent a neural axis MRI, lumbar puncture and blood samples. Levels of BAFF, CHI3L1, sCD163, OPN on serum and CSF were analyzed by Luminex xMAP system, with a kit 11-plex ad hoc.
The CSF CHI3L1, sCD163 and OPN levels were significantly higher in MS patients than in controls. We did not find significant differences in serum CHI3L1, sCD163 and OPN levels, nor CSF or serum BAFF levels between patient and control groups. We found significantly higher CSF level of sCD163 and CHI3L1 in all patients' subgroups compared with controls, while OPN was higher in CIS and RR subgroups. We did not find significant differences for serum and CSF levels of all the markers between patients with or without clinical or radiological disease activity. CSF sCD163 and CHI3L1 levels was significant higher in CIS patients who converted to MS (p < 0.05). Using ROC curve analysis, CSF sCD163 resulted the best predictive factor. CSF CHI3L1 and OPN levels resulted useful independent predictors too. Combined ROCs of those three analytes demonstrated a better predictive value, with sCD163 and CHI3L1 resulting as the best combination.
CSF sCD163 CHI3L1 and OPN levels were higher in MS patients whereas serum CHI3L1, sCD163 and OPN levels did not show differences compared with controls. This finding confirms the high CSF specificity with regards to the analysis of processes, inflammatory and non-inflammatory, that occur within the CNS.
多发性硬化症（MS）是一种慢性、免疫介导的炎症性、神经退行性疾病。许多研究都在探讨体液生物标志物作为预测因子的潜在作用，以早期识别处于 MS 高风险的具有临床孤立综合征（CIS）的患者，或识别处于 MS 高风险的 RRMS 患者。
评估 BAFF、几丁质酶 3 样蛋白 1（CHI3L1）、sCD163、骨桥蛋白（OPN）在血清和脑脊液（CSF）中的水平与疾病活动度和进展之间的相关性。我们还希望探索血清和 CSF 生物标志物水平之间可能存在的关系。
我们纳入了 2014 年 6 月至 2016 年 6 月期间的 82 名患者。其中 71 名患者被诊断为中枢神经系统脱髓鞘疾病（46 名 RRMS 和 25 名 CIS），11 名患者患有其他神经系统疾病。所有患者均接受了神经轴 MRI、腰椎穿刺和血液样本检查。采用 Luminex xMAP 系统和专用 11 plex 试剂盒分析血清和 CSF 中的 BAFF、CHI3L1、sCD163、OPN 水平。
MS 患者的 CSF CHI3L1、sCD163 和 OPN 水平明显高于对照组。患者组和对照组之间血清 CHI3L1、sCD163 和 OPN 水平均无显著差异，CSF 或血清 BAFF 水平也无显著差异。与对照组相比，所有患者亚组的 CSF sCD163 和 CHI3L1 水平均显著升高，而 CIS 和 RR 亚组的 OPN 水平升高。我们没有发现具有临床或放射学疾病活动的患者和无疾病活动的患者之间的血清和 CSF 标志物水平存在显著差异。在转化为 MS 的 CIS 患者中，CSF sCD163 和 CHI3L1 水平显著升高（p<0.05）。使用 ROC 曲线分析，CSF sCD163 是最佳的预测因子。CSF CHI3L1 和 OPN 水平也是独立的有用预测因子。这三种分析物的联合 ROC 显示出更好的预测价值，其中 sCD163 和 CHI3L1 是最佳的组合。
MS 患者的 CSF sCD163、CHI3L1 和 OPN 水平较高，而血清 CHI3L1、sCD163 和 OPN 水平与对照组相比无差异。这一发现证实了 CSF 分析具有较高的特异性，可用于研究中枢神经系统内发生的炎症和非炎症过程。
