电子T1主机lipidome RT老杂志文章and tuberculosis treatment failure JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2004532 DO 10.1183/13993003.04532-2020 VO 59 IS 1 A1 Shivakoti, Rupak A1 Newman, John W. A1 Hanna, Luke Elizabeth A1 Queiroz, Artur T.L. A1 Borkowski, Kamil A1 Gupte, Akshay N. A1 Paradkar, Mandar A1 Satyamurthi, Pattabiraman A1 Kulkarni, Vandana A1 Selva, Murugesh A1 Pradhan, Neeta A1 Shivakumar, Shri Vijay Bala Yogendra A1 Natarajan, Saravanan A1 Karunaianantham, Ramesh A1 Gupte, Nikhil A1 Thiruvengadam, Kannan A1 Fiehn, Oliver A1 Bharadwaj, Renu A1 Kagal, Anju A1 Gaikwad, Sanjay A1 Sangle, Shashikala A1 Golub, Jonathan E. A1 Andrade, Bruno B. A1 Mave, Vidya A1 Gupta, Amita A1 Padmapriyadarsini, Chandrasekaran YR 2022 UL //www.qdcxjkg.com/content/59/1/2004532.abstract AB Introduction Host lipids play important roles in tuberculosis (TB) pathogenesis. Whether host lipids at TB treatment initiation (baseline) affect subsequent treatment outcomes has not been well characterised. We used unbiased lipidomics to study the prospective association of host lipids with TB treatment failure.Methods A case–control study (n=192), nested within a prospective cohort study, was used to investigate the association of baseline plasma lipids with TB treatment failure among adults with pulmonary TB. Cases (n=46) were defined as TB treatment failure, while controls (n=146) were those without failure. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Adjusted least-square regression was used to assess differences in groups. In addition, machine learning identified lipids with highest area under the curve (AUC) to classify cases and controls.Results Baseline levels of 32 lipids differed between controls and those with treatment failure after false discovery rate adjustment. Treatment failure was associated with lower baseline levels of cholesteryl esters and oxylipin, and higher baseline levels of ceramides and triglycerides compared to controls. Two cholesteryl ester lipids combined in a unique classifier model provided an AUC of 0.79 (95% CI 0.65–0.93) in the test dataset for prediction of TB treatment failure.Conclusions We identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. In addition, a lipid signature with prognostic accuracy for TB treatment failure was identified. These lipids could be potential targets for risk-stratification, adjunct therapy and treatment monitoring.In this study, unbiased lipidomics were used to identify host lipids prospectively associated with TB treatment failure. These lipids, some with known roles in TB pathogenesis, could be potential targets for adjunct therapy and treatment monitoring. https://bit.ly/3vHZ0Ec