TY - JOUR
T1 - Host lipidome and tuberculosis treatment failure
AU - Shivakoti, Rupak
AU - Newman, John W.
AU - Hanna, Luke Elizabeth
AU - Queiroz, Artur T.L.
AU - Borkowski, Kamil
AU - Gupte, Akshay N.
AU - Paradkar, Mandar
AU - Satyamurthi, Pattabiraman
AU - Kulkarni, Vandana
AU - Selva, Murugesh
AU - Pradhan, Neeta
AU - Shivakumar, Shri Vijay Bala Yogendra
AU - Natarajan, Saravanan
AU - Karunaianantham, Ramesh
AU - Gupte, Nikhil
AU - Thiruvengadam, Kannan
AU - Fiehn, Oliver
AU - Bharadwaj, Renu
AU - Kagal, Anju
AU - Gaikwad, Sanjay
AU - Sangle, Shashikala
AU - Golub, Jonathan E.
AU - Andrade, Bruno B.
AU - Mave, Vidya
AU - Gupta, Amita
AU - Padmapriyadarsini, Chandrasekaran
N1 - Publisher Copyright:
Copyright © The authors 2022.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85118240410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118240410&partnerID=8YFLogxK
U2 - 10.1183/13993003.04532-2020
DO - 10.1183/13993003.04532-2020
M3 - Article
C2 - 34375300
AN - SCOPUS:85118240410
SN - 0903-1936
VL - 59
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 1
M1 - 2004532
ER -