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目的 探讨脑脊液（cerebrospinal fluid, CSF）和血清中结核性脑膜炎（tuberculous meningitis, TBM）特异性生物标志物对儿童TBM的鉴别诊断价值。方法 采用前瞻性研究方法，将2020年11月至2022年11月期间在西安交通大学附属儿童医院就诊的46例确诊/疑似TBM患儿和48例非TBM患儿纳入研究。采用多重细胞因子芯片平台检测血清和CSF中69种生物标志物的浓度，包括7种既往研究报道对成人肺结核诊断有价值的生物标志物。结果 在7种成人结核病诊断标志物中，仅补体因子H在儿童TBM鉴别中具有一定的临床意义，受试者工作特征曲线下面积（area under curve,AUC）为0.805(95%CI:0.715～0.894;P <0.001)。此外，基于4种标志物（趋化因子C-C-基元配体1、补体C5、纤溶酶原激活物抑制剂1和基质金属蛋白酶9）构建的新联合模型对儿童TBM诊断潜力显著，留一交叉验证后AUC为0.954(95%CI:0.907～1.000)，灵敏度和特异度分别为92.9%和88.9%。在血清中验证，该联合模型的AUC为0.824(95%CI:0.740～0.907)，但诊断效能低于CSF蛋白模型（P <0.05）。结论 成人结核病标志物可能不适用于儿童TBM诊断。本研究提出的趋化因子C-C-基元配体1、补体C5、纤溶酶原激活物抑制剂1及基质金属蛋白酶9联合模型有望成为儿童TBM的鉴别诊断工具，且CSF样本的诊断价值优于血清样本。
Abstract：Objective To investigate the diagnostic value of tuberculosis meningitis(TBM)-specific biomarkers in cerebrospinal fluid(CSF) and serum for differentiating pediatric TBM. Methods A prospective study was conducted, enrolling 46 children with confirmed/suspected TBM and 48 non-TBM controls. A multiplex cytokine chip platform was used to measure the concentrations of 69 biomarkers in serum and CSF, including seven previously reported biomarkers with diagnostic potential for adult pulmonary tuberculosis. Results Among the seven adult tuberculosis biomarkers, only complement factor H demonstrated modest clinical significance in distinguishing pediatric TBM, with an area under the receiver operating characteristic curve(AUC) of 0.805(95%CI: 0.715-0.894; P <0.001). Furthermore, a novel combined model based on four biomarkers(C-C motif chemokine ligand 1, complement C5, plasminogen activator inhibitor-1, and matrix metalloproteinase-9) showed significant diagnostic potential for pediatric TBM. After leave-one-out cross-validation, the AUC reached 0.954(95%CI: 0.907-1.000), with sensitivity and specificity of 92.9% and 88.9%, respectively. When validated in serum, the combined model achieved an AUC of 0.824(95%CI: 0.740-0.907),but its diagnostic performance was inferior to that of the CSF protein model(P <0.05). Conclusions Adult tuberculosis biomarkers may not be suitable for diagnosing pediatric TBM. The proposed combined model of C-C motif chemokine ligand 1, complement C5,plasminogen activator inhibitor-1, and matrix metalloproteinase-9 shows promise as a diagnostic tool for pediatric TBM, with CSF samples offering superior diagnostic value over serum samples.
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基本信息:
DOI：
中图分类号:R529.3
引用信息:
[1]李少宁,蔡玉香,齐薛浩.宿主脑脊液和血清蛋白标志物在儿童结核性脑膜炎鉴别诊断中的潜力[J].传染病信息,2025,38(03):215-220.
基金信息:
西藏自治区自然科学基金组团式援藏医学项目[XZ2020ZR-ZY92(Z)]