Abstract
介绍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.
方法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.
ResultsBaseline 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.
ConclusionsWe 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.
Abstract
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
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Author contributions: R. Shivakoti designed the study, oversaw the scientific and logistical aspects of the study, and wrote the primary version of the manuscript. J.W. Newman, K. Borkowski and O. Fiehn conducted the laboratory assessments of lipids, data processing and provided interpretation of the findings. J.W. Newman and K. Borkowski also conducted the data analysis and contributed to manuscript writing and review. L.E. Hanna, A.N. Gupte, M. Paradkar, P. Satyamurthi, V. Kulkarni, M. Selva, N. Pradhan, S.V.B.Y. Shivakumar, S. Natarajan, R. Karunaianantham, N. Gupte, K. Thiruvengadam, R. Bharadwaj, A. Kagal, S. Gaikwad, S. Sangle, J.E. Golub and V. Mave contributed to cohort study design and implementation, data collection and data management. A.T.L. Queiroz and B.B. Andrade helped with the data analysis, created the statistical scripts used to plots the analyses and graphs, and also provided interpretation of the findings. A. Gupta and C. Padmapriyadarsini led the parent study design, and also contributed to the design, implementation and interpretation of this study. All authors read and approved the final manuscript.
利益冲突:R。Shivakoti在研究过程中报告了NIH的赠款。
Conflict of interest: J.W. Newman has nothing to disclose.
Conflict of interest: L.E. Hanna has nothing to disclose.
利益冲突:A.T.L.Queiroz没有什么可披露的。
Conflict of interest: K. Borkowski has nothing to disclose.
利益冲突:A.N。古普特没有什么可披露的。
Conflict of interest: M. Paradkar has nothing to disclose.
Conflict of interest: P. Satyamurthi has nothing to disclose.
利益冲突:V。Kulkarni没有什么可披露的。
Conflict of interest: M. Selva has nothing to disclose.
Conflict of interest: N. Pradhan has nothing to disclose.
Conflict of interest: S.V.B.Y. Shivakumar has nothing to disclose.
利益冲突:S。Natarajan无话可说。
Conflict of interest: R. Karunaianantham has nothing to disclose.
Conflict of interest: N. Gupte has nothing to disclose.
Conflict of interest: K. Thiruvengadam has nothing to disclose.
Conflict of interest: O. Fiehn has nothing to disclose.
利益冲突:R。Bharadwaj无话可说。
Conflict of interest: A. Kagal has nothing to disclose.
利益冲突:S。Gaikwad无需透露。
利益冲突:S。Sangle无话可说。
Conflict of interest: J.E. Golub has nothing to disclose.
Conflict of interest: B.B. Andrade has nothing to disclose.
Conflict of interest: V. Mave reports grants from NIH, during the conduct of the study.
利益冲突:A。Gupta在研究过程中报告了NIH的赠款。
利益冲突:C。Padmapriyadarsini没有什么可披露的。
支持声明:父母研究的C -Th和本手稿中的数据是作为结核病的区域前瞻性观察研究(报告)印度财团的一部分。该项目全部或部分资金由印度政府(GOI)生物技术部(DBT),印度医学研究委员会(ICMR),美国国立国家卫生研究院(NIH),美国国立卫生研究院过敏和传染病(NIAID),艾滋病研究办公室,部分由CRDF Global(USB1-31147-XX13 CRDF/NIH)分发。任何提及商业名称,商业项目或组织都不意味着任何赞助组织的认可。NIAID(UM1AI069465和R01AI097494),NICHD(R00HD089753),Gilead Foundation,Ujala Foundation,Ujala Foundation和Fogarty International Center International Center International Center BJGMC-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU-JHU HIV-TB PROGOM(D43TW0095744)也支持了本出版物中报道的研究。约翰·霍普金斯大学医学院基金和哥伦比亚大学流行病学基金进一步支持这项工作。BBA得到了Fiocruz和美国国立卫生研究院(U01AI115940)和NIH/CRDF报告国际补充基金的壁内研究计划的支持。一个。Gupte得到了由NIH Fogarty International Center资助的NIH研究培训拨款#D43 TW009340。B.B. Andrade是巴西Conselho Nacional de desenvolvimentocientíficficoeTecnológico(CNPQ)的高级研究员。 Additional support was provided to O. Fiehn by NIH U24 DK097154 and to J.W. Newman by USDA Intramural Projects 2032-51530-022-00D and 2032-51530-025-00D. The USDA is an equal opportunity employer and provider. Funding information for this article has been deposited with theCrossref Funder Registry.
- 已收到December 15, 2020.
- AcceptedMay 24, 2021.
- 复制right ©The authors 2022. For reproduction rights and permissions contactpermissions{at}ersnet.org