AUTHOR=Huang Mailing , Ding Zeyu , Li Wensheng , Chen Weibi , Du Yadong , Jia Hongyan , Sun Qi , Du Boping , Wei Rongrong , Xing Aiying , Li Qi , Chu Naihui , Pan Liping 

TITLE=Identification of protein biomarkers in host cerebrospinal fluid for differential diagnosis of tuberculous meningitis and other meningitis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.886040

DOI=10.3389/fneur.2022.886040

ISSN=1664-2295

ABSTRACT=Background and purpose: The diagnosis of tuberculous meningitis (TBM) is difficult due to the lack of sensitive methods. Identification of TBM-specific biomarkers in the cerebrospinal fluid (CSF) may help diagnose and improve our understanding of TBM pathogenesis. 
Patients and methods: Of the 112 suspected patients with TBM prospectively enrolled in the study, 32 patients with inconclusive diagnosis, non-infectious meningitis and long-term treatment with hormones and immunosuppressants, were excluded. The expression of 8 proteins in the CSF were analyzed using ELISA in 22 patients with definite TBM, 18 patients with probable TBM and 40 non-TBM patients.
Results: Significant differences in the expression of 7 proteins were detected between the TBM and non-TBM groups (P < 0.01). Unsupervised hierarchical clustering (UHC) analysis revealed a disease-specific profile consisting of 7 differentially expressed proteins for TBM diagnosis, with an accuracy of 82.5% (66/80). Logistic regression with forward stepwise analysis indicated that a combination of 3 biomarkers (APOE_APOAI_S100A8) showed a better ability to discriminate TBM from non-TBM patients [AUC = 0.916 (95%CI: 0.857 – 0.976)], with a sensitivity of 95.0% (95%CI: 83.1% – 99.4%) and a specificity of 77.5% (95%CI: 61.5% – 89.2%). 
Conclusions: Our results confirmed the potential ability of CSF proteins to distinguish TBM from non-TBM patients, and provided a useful panel for the diagnosis of TBM.