摘要
目的探讨颗粒蛋白前体(progranulin,PGRN)、神经丝轻链蛋白(neurofilament light chain,NfL)和维生素D及其受体(vitamin D receptor,VDR)在临床孤立综合征(clinically isolated syndrome,CIS)患者发病及转归中的预测价值。方法收集2017年12月至2021年12月作者医院收治的96例CIS患者,其中男33例,女63例,年龄(33.13±8.86)岁;另收集性别、年龄和长期居住地与CIS患者相匹配的神经系统非炎症疾病(non-inflammatory neurological disease,NIND)患者30例为对照组,其中男11例,女19例,年龄(31.17±5.78)岁。采用酶联免疫吸附试验法(enzyme-linked immunosorbent assay,ELISA)检测纳入者和首次转归为多发性硬化(multiple sclerosis,MS)患者的血清和脑脊液PGRN、NfL水平,淋巴细胞上清液中VDR水平。采用超高效液相色谱-串联质谱法检测外周血上清液中维生素D水平[维生素D水平=25(OH)D2水平+25(OH)D_(3)水平]。对CIS患者进行每个月电话随访1次,3个月门诊随访1次,监测血常规、肝肾功能,如出现临床转归,行头和脊髓MRI检查。结果随访时间12~38个月,中位数为24个月。57例CIS患者转归为MS(59.38%)。与NIND组比较,CIS患者血清和脑脊液PGRN水平(血清:t=-2.746,P=0.007;脑脊液:t=-17.822,P=0.000)、NfL水平(血清:t=-17.627,P=0.000;脑脊液:t=-13.543,P=0.000)升高,血清25(OH)D_(3)(t=22.512,P=0.000)和VDR水平(t=12.315,P=0.000)降低。与未转归CIS患者相比较,转归MS的患者NfL基线水平(血清:t=25.052,P=0.000;脑脊液:t=8.362,P=0.000)增高,血清25(OH)D_(3)基线水平降低(t=-4.323,P=0.000);与转归MS前比较,转归MS后患者脑脊液PGRN水平升高(t=-5.909,P=0.000),血清维生素D(t=5.265,P=0.000)、25(OH)D_(3)水平(t=5.204,P=0.000)降低,血清和脑脊液NfL水平升高(血:t=-17.229,P=0.000;脑脊液:t=-8.949,P=0.000)。ROC分析显示,CIS患者外周血25(OH)D_(3)水平低于12.58 ng/mL、脑脊液NfL水平低于1383 pg/mL易转归为MS。结论CIS患者存在神经轴突损伤。PGRN尚不能预测CIS向MS转归,NfL是预测CIS转归为MS的潜在标志物。低维生素D水平可能是CIS致病及转归为MS的预测因素。
Objective To explore the predictive value of granule protein precursor(PGRN),neurofilament light chain protein(NfL),vitamin D and vitamin D receptors(VDR)in the pathogenesis and prognosis of clinically isolated syndrome(CIS)patients.Methods Ninety-six cases of CIS patients admitted to our hospital from December 2017 to December 2021 were collected,including 33 males and 63 females,with an average age of(33.13±8.86)years.Thirty cases of non-inflammatory neurological disease(NIND)matching the gender,age and long-term residence of CIS patients were collected as the control group,including 11 males and 19 females,with an average age of(31.17±5.78)years.ELISA was used to detect the levels of PGRN and NfL in the serum and cerebrospinal fluid(CSF),as well as the levels of VDR in the lymphocyte supernatant of the enrolled individuals and patients who converted to multiple sclerosis(MS)for the first time.Ultra-high performance liquid chromatography tandem mass spectrometry was used to detect vitamin D levels in peripheral blood supernatant[vitamin D=25(OH)D2+25(OH)D_(3)].CIS patients were followed up by phone once a month and outpatient visits once every three months to monitor blood routine,liver and kidney function.If clinical recurrence occurs,head and spinal cord MRI examinations will be performed.Results The follow-up period was 12-38 months,with a median follow-up period of 24 months.No patients were lost to follow-up during the follow-up period.Fifty-seven CIS patients were converted to MS(59.38%).Compared with the NIND group,the levels of PGRN(blood:t=-2.746,P=0.007;CSF:t=-17.822,P=0.000)and NfL(blood:t=-17.627,P=0.000;CSF:t=-13.543,P=0.000)increased in CIS patients,while the levels of 25(OH)D_(3)(t=22.512,P=0.000)and VDR(t=12.315,P=0.000)decreased.Compared with non-recurrent CIS patients,patients who converted to MS had higher baseline levels of NfL(blood:t=25.052,P=0.000;CSF:t=8.362,P=0.000)and lower baseline levels of 25(OH)D_(3)(t=-4.323,P=0.000).Compared with before conversion to MS,patients who converted to MS showed an increase in PGRN levels in CSF(t=-5.909,P=0.000),serum levels of vitamin D(t=5.265,P=0.000)and 25(OH)D_(3)(t=5.204,P=0.000)decreased,and NfL levels in serum and cerebrospinal fluid(blood:t=-17.229,P=0.000;CSF:t=-8.949,P=0.000)increased after conversion.ROC analysis showed that CIS patients with peripheral blood 25(OH)D_(3) levels below 12.58 ng/mL and CSF NfL levels below 1383 pg/mL are more likely to convert to MS.Conclusions CIS patients have axonal injury.PGRN cannot predict the transition from CIS to MS,while NfL is a potential biomarker for predicting the transition from CIS to MS.Low vitamin D levels may be a predictive factor for CIS pathogenesis and conversion to MS.
作者
梁军利
陆梦如
丘小慧
梁津瑜
韦云飞
LIANG Junli;LU Mengru;QIU Xiaohui;LIANG Jinyu;WEI Yunfei(不详;Department of Neurology,The Second Affiliated Hospital of Guangxi Medical University,Nanning 530007,China)
出处
《中国神经免疫学和神经病学杂志》
2025年第1期28-34,共7页
Chinese Journal of Neuroimmunology and Neurology
基金
2020年度广西高校中青年教师科研基础能力提升项目(NO.2020KY03041)
2021年广西医疗卫生适宜技术开发与推广应用项目(NO.S2020015)。
