Data from: Whole blood transcriptional profiles and the pathogenesis of tuberculous meningitis

Mortality and morbidity from tuberculous meningitis (TBM) are common and closely linked to the inflammatory response triggered by Mycobacterium tuberculosis infection, though the mechanisms underlying this association are not well understood. To explore this, we aimed to identify gene modules, hubs, and pathways associated with TBM pathogenesis and mortality, and determine the best predictors of death. Using whole blood RNA sequencing, we analyzed transcriptional profiles from 281 Vietnamese adults with TBM (207 HIV-negative; 74 HIV-positive), 295 with pulmonary TB (PTB), and 30 healthy controls. Through weighted gene co-expression network and pathway analysis, we identified modules, hub genes and pathways linked to TBM severity and mortality, with a consensus analysis identifying consensual patterns between HIV-positive and HIV-negative individuals. Using multivariate elastic-net Cox regression, we selected candidate predictors of TBM mortality, then model prediction performance using logistic regression and internal bootstrap validation to choose best predictors. Increased neutrophil activation and decreased T and B cell activation pathways were linked to TBM mortality. In HIV-positive adults, death was associated with increased angiogenesis, while HIV-negative individuals exhibited heightened TNF signaling and reduced extracellular matrix organization. Four hub genes – MCEMP1, NELL2, ZNF354C, and CD4 – emerged as strong predictors of death from TBM (AUC 0.80 in HIV-negative, 0.86 in HIV-positive). Our findings suggest TBM induces a systemic inflammatory response similar to PTB, but with key gene modules, hubs and pathways strongly associated with death, offering insights for potential therapeutic targets and a novel 4-gene biomarker for predicting TBM outcomes.