【摘要】 目的 探讨临床孤立综合征(CIS)患者急性期血清及脑脊液(CSF)生物标志物水平对转归为多发性硬化(MS)的预测价值。方法 纳入2018年1月至2020年11月作者医院收治的急性期CIS患者74例，其中女性54例，男性20例，平均年龄(31.64±8.42)岁。同时纳入30例神经系统非炎性疾病(NIND)患者作为对照组。采用超高效液相色谱-串联质谱法(UHPLC-MS/MS)或ELISA法检测患者免疫治疗前血清维生素D[25(OH)D2、25(OH)D3]、维生素D受体(VDR)水平，并检测血清和CSF Th17细胞相关因子[血清白细胞介素(IL)-6、IL-17A、IL-21、IL-22、IL-23、转化生长因子-β(TGF-β)]的水平。对CIS患者进行随访，记录其转归为MS的情况。比较CIS及NIND患者、转归及未转归CIS患者，以及MS患者转归前后细胞因子水平的差异。结果 随访时间6～42个月，中位数为25个月，失访3例，43例CIS患者转归为MS。与NIND组相比，CIS组患者血清维生素D、VDR、IL-6以及血清和CSF TGF-β水平均降低(P<0.05),血清和CSF IL-17A、IL-21、IL-22、IL-23水平增高(P<0.05)。转归为MS的CIS患者治疗前CSF IL-17A、IL-23水平较未转归患者高升(P<0.05)。转归为MS的CIS患者血清和CSF中IL-17A、IL-23水平较转归前增高，血清TGF-β水平降低，IL-6水平增高，CSF中TGF-β水平升高(均P<0.05)。相关性分析显示CIS患者扩展残疾状况量表评分与血清IL-17A和IL-21水平呈负相关(r=-0.247;r=-0.256;均P<0.05),血清维生素D、VDR与血清和CSF Th17细胞相关因子无相关性(均P>0.05)。结论 CSF IL-17A和IL-23增高可能是预测CIS转归为MS的生物标志物。更多还原

【Abstract】 Objective To explore the predictive value of serum and cerebrospinal fluid(CSF) biomarkers levels in acute clinical isolated syndrome(CIS)patients transforming into multiple sclerosis(MS). Methods From January 2018 to November 2020,74 CIS patients during acute phase hospitalized in authors’ hospital were enrolled, including 54 female and 20 male with an average age of(31.64±8.42)years.At the same time, 30 patients with non-inflammatory neurological disease(NIND)were recruited as control group.The levels of vitamin D[25(OH)D2,25(OH)D3]and vitamin D receptor(VDR)in serum, Th17 cells related cytokines[interleukin(IL)-6,IL-17A,IL-21,IL-22,IL-23,transforming growth factor beta(TGF-β)]in serum and CSF before immunotherapy in patients were detected by ultrahigh performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)or enzyme-linked immunosorbent assay.The CIS patients were followed up and their conversion to MS was recorded.The differences of these cytokines were compared between CIS and NIND group, converted into MS group and unconverted group, before and after conversion to MS.Results After an follow-up for 6 to 42 months, with a median of 25 months, three patients lost in follow-up, 43 CIS patients converted into MS.Compared with NIND group, the levels of serum vitamin D,VDR and IL-6,serum and CSF TGF-β all decreased(P<0.05),as well as the serum and CSF levels of IL-17A,IL-21,IL-22 and IL-23 all increased in CIS patients(P<0.05).Before treatment, in CIS patients who converted to MS,CSF levels of IL-17A and IL-23 were higher than those in the unconverted group.CIS patients after conversion to MS showed higher levels of serum and CSF IL-17A and IL-23,lower level of serum TGF-β,and higher level of serum IL-6 and CSF TGF-β than those before conversion to MS(all P<0.05).Correlation analysis indicated that expanded disability status scale scores were negatively correlated with serum IL-17A and IL-21 levels(r=-0.247;r=-0.256;all P<0.05);however, the correlations between serum vitamin D,VDR and Th17 cells related cytokines in serum and CSF were not significant.Conclusions CSF IL-17A and IL-23 may be predictive biomarkers for CIS conversion into MS.更多还原