首页|期刊导航|临床与病理杂志|T淋巴细胞亚群联合脑脊液肝素结合蛋白对神经内科颅内感染的诊断价值及与预后的相关性

T淋巴细胞亚群联合脑脊液肝素结合蛋白对神经内科颅内感染的诊断价值及与预后的相关性OA

Diagnostic value of T lymphocyte subsets combined with cerebrospinal fluid heparin-binding protein for intracranial infection in neurology patients and their correlation with prognosis

中文摘要英文摘要

目的:神经内科颅内感染致死、致残率高,早期诊断极具挑战,亟需敏感、特异的早期生物标志物.肝素结合蛋白(heparin-binding protein,HBP)介导血脑屏障损伤与炎症级联反应,T淋巴细胞亚群反映特异性免疫应答,二者共同主导颅内感染进程,但联合应用价值尚待明确.本研究旨在探讨二者联合对神经内科颅内感染的诊断价值及与预后的相关性.方法:回顾性纳入2023年1月至2025年4月在南阳市第二人民医院神经内科诊治的疑似颅内感染患者.根据临床综合诊断,将确诊为颅内感染的患者纳入颅内感染组,非颅内感染的患者纳入对照组.根据治疗3个月后的格拉斯哥预后量表(Glasgow Outcome Scale,GOS)评分,将颅内感染的患者分为预后良好组(4~5分)和预后不良组(1~3分).入院24 h内采集所有患者的血液、脑脊液样本.采用流式细胞仪检测外周血T淋巴细胞亚群CD3+、CD4+、CD8+水平,并计算CD4+/CD8+比值.检测血常规和血清超敏C反应蛋白(high-sensitivity C reactive protein,hs-CRP)水平.采用酶联免疫吸附法检测脑脊液炎症指标,包括HBP、白介素(interleukin,IL)-1β、IL-2受体、IL-6、IL-8.采用Logistic回归分析外周血T淋巴细胞亚群、HBP对颅内感染发病风险及预后不良的影响.先进行单因素分析,然后将单因素分析中有统计学差异的变量纳入多因素Logistic回归模型,以筛选独立危险因素.绘制受试者操作特征(receiver operating characteristic,ROC)曲线,计算曲线下面积(area under the curve,AUC),以评估各指标对颅内感染的诊断效能及预后预测价值.为评估联合诊断及预后预测的价值,基于多因素Logistic回归分析结果构建联合模型,计算每个样本的预测概率,并以该预测概率为检验变量绘制联合ROC曲线,比较其与单项指标AUC的差异.结果:颅内感染组96例,对照组35例;预后不良组38例,预后良好组58例.颅内感染组患者外周血CD3+、CD4+水平及CD4+/CD8+比值显著低于对照组,而外周血CD8+水平及脑脊液HBP水平均显著高于对照组(均P<0.05),且外周血CD3⁺(OR=0.849)、CD4⁺(OR=0.828)水平升高均为神经内科颅内感染的独立保护因素,而外周血CD8+(OR=1.489)、脑脊液HBP(OR=1.189)水平升高则均为其独立风险因素(均P<0.05).ROC曲线结果显示,血清CD3+、CD4+、CD8水平与脑脊液HBP水平联合检测诊断颅内感染的效能(AUC=0.962)显著高于单项指标(AUC分别为0.812、0.827、0.750、0.866),敏感度(88.54%)和特异度(91.43%)均较高;在鉴别病毒和细菌性感染方面,联合检测效能(AUC=0.883)亦显著高于单项指标(AUC分别为0.761、0.774、0.693、0.799).此外,与预后良好组比较,预后不良组脑脊液HBP水平明显升高,血清CD4+水平、CD4+/CD8+比值均显著降低(均P<0.05),且CD4+/CD8+比值降低(OR=0.175)和脑脊液HBP水平升高(OR=1.095)均为颅内感染预后不良的独立预测因子(均P<0.05).ROC曲线结果显示,二者联合应用预测预后不良的价值(AUC=0.809)显著高于单项指标(AUC分别为0.674、0.730).结论:T淋巴细胞亚群联合脑脊液HBP可显著提升颅内感染的诊断及病原学鉴别效能,并对预后不良具有较高预测价值,临床应用前景广阔.

Objective:Intracranial infection in neurology patients is associated with high mortality and disability rates,and early diagnosis remains highly challenging,underscoring the need for sensitive and specific early biomarkers.Heparin-binding protein(HBP)mediates blood-brain barrier injury and inflammatory cascade reactions,while T lymphocyte subsets reflect specific immune responses.Together,they play critical roles in the pathogenesis of intracranial infection;however,the value of their combined application remains unclear.This study aims to investigate the predictive value of T lymphocyte subsets combined with HBP for intracranial infection and their association with prognosis. Methods:This retrospective study included patients with suspected intracranial infection who were treated in the Department of Neurology,Nanyang Second People's Hospital,between January 2023 and April 2025.According to comprehensive clinical diagnosis,patients with confirmed intracranial infection were assigned to the intracranial infection group,while those without intracranial infection served as controls.Based on the Glasgow Outcome Scale(GOS)score at 3 months after treatment,patients with intracranial infection were further divided into a favorable prognosis group(GOS score 4 to 5)and an unfavorable prognosis group(GOS score 1 to 3).Blood and cerebrospinal fluid(CSF)samples were collected from all patients within 24 hours of admission.Peripheral blood T lymphocyte subsets,including CD3+,CD4+,and CD8+T cells,were measured by flow cytometry,and the CD4+/CD8+ratio was calculated.Complete blood count and serum high-sensitivity C-reactive protein(hs-CRP)levels were determined.CSF inflammatory markers,including HBP,interleukin(IL)-1β,IL-2 receptor,IL-6,and IL-8,were measured using enzyme-linked immunosorbent assay(ELISA).Logistic regression analysis was performed to evaluate the effects of peripheral blood T lymphocyte subsets and CSF HBP on the risk of intracranial infection and unfavorable prognosis.Univariate analyses were conducted first,and variables showing statistical significance were subsequently entered into multivariate logistic regression models to identify independent risk factors.Receiver operating characteristic(ROC)curves were generated,and the area under the curve(AUC)was calculated to assess the diagnostic and prognostic performance of each indicator.To evaluate the value of combined diagnosis,a multivariate Logistic regression-based prediction model was established using independent factors identified in the multivariate analysis.Predicted probabilities were calculated for each patient and used as test variables to generate combined ROC curves,which were compared with AUCs of individual markers. Results:A total of 96 patients were included in the intracranial infection group and 35 in the control group.Among patients with intracranial infection,38 had an unfavorable prognosis,and 58 had a favorable prognosis.Compared with the control group,patients with intracranial infection had significantly lower peripheral blood CD3+and CD4+levels and a lower CD4+/CD8+ratio,whereas peripheral blood CD8+levels and cerebrospinal fluid(CSF)HBP levels were significantly higher(all P<0.05).Elevated peripheral blood CD3+(OR=0.849)and CD4+(OR=0.828)levels were identified as independent protective factors against intracranial infection,whereas elevated peripheral blood CD8+(OR=1.489)and CSF HBP(OR=1.189)levels were independent risk factors(all P<0.05).ROC curve analysis showed that the combined detection of peripheral blood CD3+,CD4+,CD8+,and CSF HBP achieved significantly better diagnostic performance for intracranial infection(AUC=0.962)than any single indicator alone(AUCs of 0.812,0.827,0.750,and 0.866,respectively),with a sensitivity of 88.54%and a specificity of 91.43%.For differentiating viral from bacterial infections,the combined model also demonstrated superior performance(AUC=0.883)compared with individual markers(AUCs of 0.761,0.774,0.693,and 0.799,respectively).Compared with the favorable prognosis group,the unfavorable prognosis group had significantly higher CSF HBP levels and significantly lower serum CD4+levels and CD4+/CD8+ratios(all P<0.05).Reduced CD4+/CD8+ratio(OR=0.175)and elevated CSF HBP level(OR=1.095)were independent predictors of unfavorable prognosis(both P<0.05).ROC curve analysis showed that the combined application of these 2 indicators increased the AUC for predicting unfavorable prognosis to 0.809,which was significantly higher than that of either indicator alone(AUCs of 0.674 and 0.730,respectively). Conclusion:The combination of T lymphocyte subsets and CSF HBP significantly improves the diagnostic accuracy and etiological differentiation of intracranial infection and provides substantial value in predicting unfavorable prognosis.This combined approach has promising clinical application prospects.

陈博;宋彦;宋小娜

南阳市第二人民医院神经内科,南阳 473000南阳市第二人民医院神经内科,南阳 473000南阳市第二人民医院神经内科,南阳 473000

医药卫生

T淋巴细胞亚群脑脊液肝素结合蛋白颅内感染诊断价值预后

T lymphocyte subsetscerebrospinal fluidheparin-binding proteinintracranial infectiondiagnostic valueprognosis

《临床与病理杂志》 2026 (4)

524-534,11

10.11817/j.issn.2095-6959.2026.250758

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