The ability of a 3-gene host signature in blood to distinguish tuberculous meningitis from other brain infections.
Huynh J., Le NHT., Nguyen BHL., Hoang HT., Do TAD., Trinh TTB., Vu DTM., Do VD., Ngiem NM., Donovan J., Nguyen PH., Dang TV., Nguyen TTA., Nguyen BD., Dang HMT., Ho NTD., Le TV., Le VH., Thwaites G., Thuong NTT.
BackgroundTuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections.MethodsThe expression of 3 genes (Dual specificity phosphatase 3- DUSP3, Guanylate-binding protein- GBP5, Krupple-like factor 2- KLF2) was analysed by RNA sequencing of archived whole blood from four cohorts of Vietnamese adults: 281 with TBM; 279 with pulmonary tuberculosis; 50 with other brain infections; and 30 healthy controls. 'TB scores' (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC).ResultsGBP5 was upregulated in TBM compared to other brain infections (p ConclusionThe 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in HIV-positive individuals. Validation in large prospective diagnostic study is now required.