Samenvatting

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.