Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers

BACKGROUND: The optimal diagnosis and treatment of tuberculosis (TB) are challenging due to underdiagnosis and inadequate treatment monitoring. Lipid-related genes are crucial components of the host immune response in TB. However, their dynamic expression and potential usefulness for monitoring response to anti-TB treatment are unclear. METHODOLOGY: In the present study, we used a targeted, knowledge-based approach to investigate the expression of lipid-related genes during anti-TB treatment and their potential use as biomarkers of treatment response. RESULTS AND DISCUSSION: The expression levels of 10 genes (ARPC5, ACSL4, PLD4, LIPA, CHMP2B, RAB5A, GABARAPL2, PLA2G4A, MBOAT2, and MBOAT1) were significantly altered during standard anti-TB treatment. We evaluated the potential usefulness of this 10-lipid-gene signature for TB diagnosis and treatment monitoring in various clinical scenarios across multiple populations. We also compared this signature with other transcriptomic signatures. The 10-lipid-gene signature could distinguish patients with TB from those with latent tuberculosis infection and non-TB controls (area under the receiver operating characteristic curve > 0.7 for most cases); it could also be useful for monitoring response to anti-TB treatment. Although the performance of the new signature was not better than that of previous signatures (i.e., RISK6, Sambarey10, Long10), our results suggest the usefulness of metabolism-centric biomarkers CONCLUSIONS: Lipid-related genes play significant roles in TB pathophysiology and host immune responses. Furthermore, transcriptomic signatures related to the immune response and lipid-related gene may be useful for TB diagnosis and treatment monitoring.