| Title: |
Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis |
| Authors: |
Dian, S; Koeken, VACM; Ardiansyah, E; Ganiem, AR; van Abeelen, K; Aguirre-Gamboa, R; Purnama, F; Imaculata, S; Annisa, J; Chaidir, L; Ruslami, R; Joosten, LAB; Netea, MG; Alisjahbana, B; van Crevel, R; van Laarhoven, A; Kumar, V |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
This study examines the role of host inflammation in the high mortality of tuberculous meningitis (TBM) and identifies potential biomarkers associated with improved survival. We conducted a case-control study involving 131 patients in a discovery cohort, 81 TBM patients in a validation cohort, and 43 non-infected controls from a referral hospital in Indonesia. We measured 94 inflammation-related proteins in cerebrospinal fluid (CSF) and performed genome-wide quantitative trait loci (QTL) mapping. Sixty-seven proteins were found to be differentially expressed between TBM patients and controls, with 64 proteins elevated in patients. Five proteins, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-10 (MMP-10), were identified as predictors of 180-day mortality in TBM patients. The validation cohort confirmed that MMP-10, but not VEGF, was predictive of mortality. Genome-wide QTL mapping identified two genome-wide significant and four suggestive genetic loci associated with CSF MMP-10, which also predicted survival in an additional cohort of 218 patients. High CSF concentrations of MMP-10, along with specific genetic loci, may be associated with survival in TBM patients, suggesting a potential role for MMP-10 in disease pathogenesis and warranting further investigation into its utility in host-directed therapies. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1093/braincomms/fcaf273 |
| DOI: |
10.1093/braincomms/fcaf273 |
| Availability: |
https://doi.org/10.1093/braincomms/fcaf273; https://ora.ox.ac.uk/objects/uuid:35cbc7b8-bb20-4dd2-804f-0f13f87bfcb4 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.7EFC6B69 |
| Database: |
BASE |