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

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

doi:10.3389/fneur.2022.886040

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

Front Neurol. 2022 Aug 8:13:886040. doi: 10.3389/fneur.2022.886040. eCollection 2022.

Authors

Mailing Huang^{1

2}, Zeyu Ding³, Wensheng Li^{2

4}, Weibi Chen⁵, Yadong Du^{1

2}, Hongyan Jia^{2

6}, Qi Sun^{2

6}, Boping Du^{2

6}, Rongrong Wei^{2

6}, Aiying Xing^{2

6}, Qi Li¹, Naihui Chu¹, Liping Pan^{2

6}

Affiliations

¹ Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China.
² Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
³ Neurology Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Department of Emergency Medicine, Beijing Chest Hospital, Capital Medical University, Beijing, China.
⁵ Neurology Department, Xuanwu Hospital, Capital Medical University, Beijing, China.
⁶ Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, China.

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 was analyzed using ELISA in 22 patients with definite TBM, 18 patients with probable TBM, and 40 patients with non-TBM.

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 patients with non-TBM [area under the curve (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%).

Conclusion: Our results confirmed the potential ability of CSF proteins to distinguish TBM from patients with non-TBM and provided a useful panel for the diagnosis of TBM.

Keywords: cerebrospinal fluid; diagnosis; infectious meningitis; protein biomarker; tuberculous meningitis.