Potential of host cerebrospinal fluid and serum protein markers in the differential diagnosis of tuberculous meningitis in children

LI Shaoning; CAI Yuxiang; QI Xuehao

doi:10.3969/j.issn.1007-8134.2025.03.002

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.