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

Abstract

Background and purposeThe 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 methodsOf 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.ResultsSignificant 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%).ConclusionOur 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.

Recent advances in understanding the human host immune response in tuberculous meningitis

“…Significantly increased whole blood transcripts and CSF concentrations of neutrophil-associated proteins including MMP, cathepsin G, lipocalin 2 and human neutrophil peptides 1-3 (α-defensins) are found in TBM-IRIS ( 48 ). S100A8, a neutrophil chemotactic protein, is differentially expressed in TBM compared to other forms of meningitis ( 57 ), and increased CSF levels of S100A8/9 accompany TBM-IRIS ( 35 ). Variations in the LTA4H genotype have been shown to predict outcomes in TBM.…”

Diagnosis of post-neurosurgical bacterial meningitis in patients with aneurysmal subarachnoid hemorrhage based on the immunity-related proteomics signature of the cerebrospinal fluid

“…Lactate and procalcitonin (PCT) in the CSF have been found to be suggestive biomarkers for the diagnosis of CNS bacterial infections and have already been clinically applied for the auxiliary diagnosis of meningitis and sepsis ( 16 , 17 ). Other molecules, such as MMP-9 and a combination of APOE/APOAI/S100A8 proteins, were also shown to play diagnostic roles in community-acquired bacterial meningitis ( 18 , 19 ). We found that some of these biomarkers were mediators in aSAH or other neurological diseases ( 20 , 21 ).…”

The diagnosis of tuberculous meningitis: advancements in new technologies and machine learning algorithms

“…The study also did not explore the relationships between CSF protein and other CSF analytes. Huang et al (2022) employed ELISA assays to examine the expression of eight proteins in the CSF of 80 patients, which included 22 confirmed cases of TBM, 18 probable cases, and 40 non-TBM cases. They discovered significant differences in the expression of seven proteins between TBM and non-TBM groups.…”