AUTHOR=Phat Nguyen Ky , Tien Nguyen Tran Nam , Anh Nguyen Ky , Yen Nguyen Thi Hai , Lee Yoon Ah , Trinh Hoang Kim Tu , Le Kieu-Minh , Ahn Sangzin , Cho Yong-Soon , Park Seongoh , Kim Dong Hyun , Long Nguyen Phuoc , Shin Jae-Gook 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1210372

DOI=10.3389/fimmu.2023.1210372

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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. </p></sec><sec><title>Methodology</title><p>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. </p></sec><sec><title>Results and discussion</title><p>The expression levels of 10 genes (<italic>ARPC5</italic>, <italic>ACSL4</italic>, <italic>PLD4</italic>, <italic>LIPA</italic>, <italic>CHMP2B</italic>, <italic>RAB5A</italic>, <italic>GABARAPL2</italic>, <italic>PLA2G4A</italic>, <italic>MBOAT2</italic>, and <italic>MBOAT1</italic>) 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 &gt; 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</p></sec><sec><title>Conclusions</title><p>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.</p></sec>