脑脊液细胞因子在帕金森病和非典型帕金森综合征鉴别诊断中的价值

The evaluation of cerebrospinal fluid cytokines in the differential diagnosis of Parkinson disease and atypical parkinsonism

目的测定帕金森病(Parkinson disease,PD)、多系统萎缩(multiple system atrophy,MSA)、进行性核上性麻痹(progressive supranuclear palsy,PSP)患者与对照组脑脊液(cerebrospinal fluid,CSF)细胞因子水平,并探讨其在疾病鉴别诊断中的价值。方法采用酶联免疫吸附法测定34例PD、18例MSA、23例PSP患者和29例对照组CSF中C-反应蛋白(C-reactive protein,CRP)、白介素(interleukin,IL)-1β(IL-1β)、IL-4、IL-6、IL-10、IL-18、肿瘤坏死因子(tumor necrosis factor,TNF)-α、干扰素(interferon,IFN)-γ和转化生长因子(transforming growth factor,TGF)-β浓度,并使用受试者工作特征曲线分析诊断价值。结果与PD组相比,PSP组CSF中CRP(8766.96±4250.87 vs.5104.33±3843.32 pg/mL)、IL-1β(4.48±2.19 vs.2.35±1.64 pg/mL),TNF-α(124.05±61.90 vs.73.26±45.74 pg/mL),IL-6(84.28±51.29 vs.45.50±37.89 pg/mL)和IL-4(4.60±2.42 vs.2.22±1.43 pg/mL)的浓度增加(P<0.05)。拟合IFN-γ和IL-4生成联合预测因子Pre 1可达PD和PSP最佳诊断效能[曲线下面积(area under curve,AUC)为0.881],Pre 1大于截断值提示PD可能。拟合IFN-γ、IL-1β和TGF-β生成联合预测因子Pre 2可达PD和MSA最佳诊断效能(AUC为0.956),Pre 2大于截断值提示PD可能。结论CSF的IFN-γ和IL-4构建的Pre 1因子升高有助于临床诊断PD而非PSP,IFN-γ、IL-1β和TGF-β构建的Pre 2因子升高对诊断PD而非MSA有一定临床价值。

Objective To quantify the levels of cytokines in the cerebrospinal fluid(CSF)of patients with Parkinson's disease(PD),Multiple system atrophy(MSA)and Progressive supranuclear palsy(PSP)and healthy controls,and investigate the value of CSF cytokines in the differential diagnosis of PD,MSA and PSP.Methods The CSF C-reactive protein(CRP),Interleukin(IL)-1β,IL-4,IL-6,IL-10,IL-18,Tumor Necrosis Factor(TNF)-α,Interferon(IFN)-γand Transforming growth factor(TGF)-βlevels in 34 PD patients,18 MSA patients,23 PSP patients and 29 healthy controls were measured using enzyme-linked immunosorbent assay.The receiver operating characteristic curve was used to analyze the diagnostic value of these cytokines.Results The CSF CRP(8766.96±4250.87 vs.5104.33±3843.32 pg/mL),IL-1β(4.48±2.19 vs.2.35±1.64 pg/mL),TNF-α(124.05±61.90 vs.73.26±45.74 pg/mL),IL-6(84.28±51.29 vs.45.50±37.89 pg/mL)and IL-4(4.60±2.42 vs.2.22±1.43 pg/mL)levels of PSP group were higher than those in PD group(P<0.05).The best diagnostic discrimination(area under curve(AUC)=0.88)between PD and PSP patients was obtained by fitting a combined predictor Pre1 from a subset of cytokines(IFN-γand IL-4),and patients whose Pre1 greater than cut-off value are considered PD.The combined predictor Pre2 from subset of cytokines(IFN-γ,IL-1βand TGF-β)could reach the best diagnostic discrimination between PD and MSA patients(AUC=0.96),and patients whose Pre2 greater than cut-off value are considered PD.Conclusions The elevated Pre1(from CSF IFN-γand IL-4)leads to a clinical diagnosis of PD but not PSP,and elevated Pre2(from CSF IFN-γ,IL-1βand TGF-β)has certain clinical value in diagnosing PD but not MSA.