Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis
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.
Authors
- Valerie A. C. M. Koeken (ORCID: https://orcid.org/0000-0002-5783-9013)
- Sofiati Dian (ORCID: https://orcid.org/0000-0001-9909-4171)
- Mihai Gheorghe Netea (ORCID: https://orcid.org/0000-0003-2421-6052)
- Raúl Aguirre‐Gamboa (ORCID: https://orcid.org/0000-0003-2505-3574)
- Leo A. B. Joosten (ORCID: https://orcid.org/0000-0001-6166-9830)
- Ahmad Rizal Ganiem (ORCID: https://orcid.org/0000-0002-0290-2759)
- Vinod Kumar (ORCID: https://orcid.org/0000-0002-2775-6049)
- Arjan van Laarhoven (ORCID: https://orcid.org/0000-0002-6607-4075)
- Bachti Alisjahbana (ORCID: https://orcid.org/0000-0003-3745-8229)
- Feby Purnama
- Sofia Imaculata (ORCID: https://orcid.org/0000-0002-1287-8895)
- Jessi Annisa
- Edwin Ardiansyah (ORCID: https://orcid.org/0000-0003-2702-5497)
- Rovina Ruslami (ORCID: https://orcid.org/0000-0003-4995-5054)
- Lidya Chaidir (ORCID: https://orcid.org/0000-0001-5661-4050)
- Reinout van Crevel
- Kirsten van Abeelen
Institutions
- University Medical Center Groningen (NL)
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- University of Groningen (NL)
- Angkor Hospital for Children (KH)
- Radboud University Medical Center (NL)
- Dr. Hasan Sadikin General Hospital (ID)
- Radboud Institute for Molecular Life Sciences (NL)
- Padjadjaran University (ID)
Publication Details
- Journal
- Brain Communications
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1093/braincomms/fcaf273
- Citations
- 2
- Primary Topic
- Infectious Diseases and Tuberculosis
- Type
- article
- Field-Weighted Citation Impact
- 4.01
Funders
- United States Agency for International Development
- Koninklijke Nederlandse Akademie van Wetenschappen
- Radboud Universiteit
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek