Frontiers in Immunology (Oct 2023)
Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers
Abstract
BackgroundThe 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. MethodologyIn 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 discussionThe 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 biomarkersConclusionsLipid-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.
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