脑脊液细胞因子水平对临床孤立综合征患者复发及 转归为多发性硬化的预测价值
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北京市卫生系统高层次人才(学科骨干)(2014-3-052);北京市自然科学基金面上项目 (7162208)


Predictive value of levels of cerebrospinal fluid cytokines on relapse and conversion to multiple sclerosis of patients with clinical isolated syndrome
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    摘要:

    目的 探讨临床孤立综合征(CIS)患者急性期脑脊液白细胞介素6(IL-6)等10 种细胞因子 水平对疾病复发和转归为多发性硬化(MS)的预测价值。方法 回顾性连续纳入2015 年1 月至2017 年 8 月在首都医科大学附属北京天坛医院住院的急性期CIS 患者33 例,其中男9 例,女24 例,中位入组年 龄35 岁。使用Luminex 液相芯片法检测脑脊液细胞因子白介素(IL)-6、IL-4、IL-2、IL-10、IL-13、IL-17A、 IL-21、IL-23、干扰素γ(IFN-γ)水平;使用酶联免疫吸附测定法检测转化生长因子β1(TGF-β1)水平。 对患者进行门诊随访,记录其复发、转归为MS 的情况。比较复发及未复发者脑脊液细胞因子的差异。 采用受试者工作特征(ROC)曲线及Cox 回归模型分析脑脊液细胞因子对CIS 患者复发及转归为MS 的预 测价值。结果 入组患者随访时间为10.7~39.9 个月,中位随访时间23.4(17.6,29.1)个月。11 例(33.3%) 患者在随访期出现临床复发,其中4 例诊断为MS。另有2 例患者虽然未出现临床复发,但随访MR 发现 新发病灶最终诊断为MS。复发的CIS 患者首次发病时脑脊液IL-6 水平显著高于未复发的CIS 患者[1.9 (1.4,7.9)ng/L 比1.1(0.9,1.5)ng/L;Z=-2.904,P=0.003]。ROC 曲线分析显示,IL-6 在判断复发时最佳临界 值为1.37 ng/L。单因素Cox 回归结果显示,脑脊液IL-6 > 1.37 ng/L 不能预测CIS 复发(HR=1.54,95%CI: 0.40~5.92,P=0.533)。转归为MS 和未转归为MS 的CIS 患者首次发病急性期脑脊液IL-6 等10 种细胞因 子水差异均无统计学意义(均P> 0.05)。结论 本研究所观察的脑脊液IL-6 等10 种细胞因子可能不是 预测CIS 患者复发或转归为MS 的标志物。

    Abstract:

    Objective To investigate the predictive value of levels of ten cerebrospinal fluid( CSF) cytokines including interleukin-6( IL-6) on relapse and conversion to multiple sclerosis( MS) of patients with clinical isolated syndrome( CIS). Methods A total of 33 patients with acute CIS admitted to Beijing Tiantan Hospital Affiliated to Capital Medical University from January 2015 to August 2017 were retrospectively enrolled, including 9 males and 24 females, with a median age of 35 years old. The CSF levels of IL-6, IL-4, IL-2, IL-10, IL-13, IL-17A, IL-21, IL-23, and interferon-γ( IFN-γ) were detected by Luminex liquid chip method. The level of transforming growth factor beta 1( TGF-β1) was detected by enzyme-linked immunosorbent assay( ELISA). The patients were followed up in outpatient service, and the relapse and conversion to MS were recorded. The difference of CSF cytokines between relapse and non relapse patients was compared. Receiver operating characteristic( ROC) curve and Cox regression models were used to analyze the predictive value of CSF cytokines on the the relapse and conversion to MS of CIS patients. Results The median follow-up time of the enrolled patients was 23.4( 17.6, 29.1) months. 11 CIS cases( 33.3%) had clinical relapse during the follow-up period, and 4 cases were diagnosed as MS. Although no clinical recurrence was found in other 2 patients, follow-up MR revealed new lesions, which were diagnosed as MS. The level of CSF IL-6 in patients with relapse was significantly higher than that in patients without relapse[ 1.9( 1.4,7.9) ng/L vs. 1.1( 0.9,1.5) ng/L; Z=-2.904,P=0.003]. ROC curve analysis showed that the optimal cut-off value of IL-6 was 1.37 ng/L. However, Uni-variate Cox regression showed that CSF IL-6 > 1.37 ng/L could not predict the relapse of CIS (HR=1.54, 95%CI: 0.40-5.92,P=0.533). There was no significant difference in CSF IL-6 and the other 9 cytokines between the patients with conversion to MS and those without conversion to MS( all P > 0.05). Conclusions Ten cytokines such as IL-6 in CIF investigated in this study may not be markers for predicting the relapse or conversion to MS of CIS patients.

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魏玉桢 苌浩晓 杜利 李昕頔 刘翕然 徐芸 尹琳琳 张星虎.脑脊液细胞因子水平对临床孤立综合征患者复发及 转归为多发性硬化的预测价值[J].神经疾病与精神卫生,2020,20(8):
DOI :10.3969/j. issn.1009-6574.2020.08.008.

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  • 在线发布日期: 2020-12-07