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Host lipidome and tuberculosis treatment failure
European Respiratory Journal ( IF 24.3 ) Pub Date : 2022-01-06 , DOI: 10.1183/13993003.04532-2020
Rupak Shivakoti 1, 2 , John W Newman 3, 4, 5 , Luke Elizabeth Hanna 6 , Artur T L Queiroz 7, 8 , Kamil Borkowski 5 , Akshay N Gupte 9 , Mandar Paradkar 10 , Pattabiraman Satyamurthi 6 , Vandana Kulkarni 10 , Murugesh Selva 6 , Neeta Pradhan 10 , Shri Vijay Bala Yogendra Shivakumar 11 , Saravanan Natarajan 6 , Ramesh Karunaianantham 6 , Nikhil Gupte 9, 10 , Kannan Thiruvengadam 6 , Oliver Fiehn 5 , Renu Bharadwaj 12 , Anju Kagal 12 , Sanjay Gaikwad 12 , Shashikala Sangle 12 , Jonathan E Golub 9 , Bruno B Andrade 7, 8, 13, 14, 15, 16 , Vidya Mave 9, 10 , Amita Gupta 9, 10, 17 , Chandrasekaran Padmapriyadarsini 6, 17
Affiliation  

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.



中文翻译:

宿主脂质组和结核病治疗失败

介绍

宿主脂质在结核病 (TB) 发病机制中起重要作用。结核病治疗开始时(基线)的宿主脂质是否会影响随后的治疗结果尚未得到很好的表征。我们使用无偏脂质组学来研究宿主脂质与结核病治疗失败的前瞻性关联。

方法

一项嵌套在前瞻性队列研究中的病例对照研究(n=192)用于研究基线血脂与成人肺结核患者结核病治疗失败的关系。病例(n = 46)被定义为结核病治疗失败,而对照(n = 146)是那些没有失败的病例。使用液相色谱质谱技术测量复合脂质和炎症脂质介质。调整后的最小二乘回归用于评估组间的差异。此外,机器学习识别出曲线下面积 (AUC) 最高的脂质,以对病例和对照进行分类。

结果

在错误发现率调整后,对照组和治疗失败的 32 种脂质的基线水平存在差异。与对照组相比,治疗失败与较低的胆固醇酯和羟脂基线水平以及较高的神经酰胺和甘油三酯基线水平有关。在一个独特的分类器模型中结合两种胆固醇酯脂质,在用于预测结核病治疗失败的测试数据集中提供了 0.79(95% CI 0.65-0.93)的 AUC。

结论

我们确定了与结核病治疗失败相关的脂质,其中一些在结核病发病机制中具有已知作用。此外,还确定了对结核病治疗失败具有预后准确性的脂质特征。这些脂质可能是风险分层、辅助治疗和治疗监测的潜在目标。

更新日期:2022-01-06
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