The Ability of a 3-Gene Host Signature in Blood to Distinguish Tuberculous Meningitis From Other Brain Infections

• Published in: The Journal of infectious diseases 2024-08, Vol.230 (2), p.e268-e278
• Main Authors: Huynh, Julie, Nhat, Le Hoang Thanh, Bao, Nguyen Le Hoai, Hai, Hoang Thanh, Thu, Do Dang Anh, Tram, Trinh Thi Bich, Dung, Vu Thi Mong, Vinh, Do Dinh, Ngoc, Nghiem My, Donovan, Joseph, Phu, Nguyen Hoan, Van Thanh, Dang, Thu, Nguyen Thi Anh, Bang, Nguyen Duc, Ha, Dang Thi Minh, Nghia, Ho Dang Trung, Van Tan, Le, Van, Le Hong, Thwaites, Guy, Thuong, Nguyen Thuy Thuong
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers - blood; Blood; Diagnosis, Differential; Female; Gene expression; GTP-Binding Proteins - genetics; Guanylate-binding protein; HIV; Human immunodeficiency virus; Humans; Infections; Krueppel-like factor; Kruppel-Like Transcription Factors - genetics; Major; Male; Medical diagnosis; Meningitis; Middle Aged; ROC Curve; Tuberculosis; Tuberculosis, Meningeal - blood; Tuberculosis, Meningeal - diagnosis; Tuberculosis, Meningeal - genetics; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - genetics; Vietnam; Young Adult
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiad606

Abstract Background Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections. Methods The expression of 3 genes (dual specificity phosphatase 3 [DUSP3], guanylate-binding protein [GBP5], krupple-like factor 2 [KLF2]) was analyzed by RNA sequencing of archived whole blood from 4 cohorts of Vietnamese adults: 281 with TBM, 279 with pulmonary tuberculosis, 50 with other brain infections, and 30 healthy controls. Tuberculosis scores (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC). Results GBP5 was upregulated in TBM compared to other brain infections (P < .001), with no difference in DUSP3 and KLF2 expression. The diagnostic performance of GBP5 alone (AUC, 0.74; 95% confidence interval [CI], .67–.81) was slightly better than the 3-gene tuberculosis score (AUC, 0.66; 95% CI, .58–.73) in TBM. Both GBP5 expression and tuberculosis score were higher in participants with human immunodeficiency virus (HIV; P < .001), with good diagnostic performance of GBP5 alone (AUC, 0.86; 95% CI, .80–.93). Conclusions The 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in individuals with HIV. Validation in large prospective diagnostic study is now required. Host immune signatures to diagnose tuberculosis show promise, but have not been investigated in tuberculous meningitis. We demonstrate the ability of a whole-blood 3-gene host signature to discriminate tuberculous meningitis from other brain infections, including individuals with HIV.