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代谢组学分析显示儿童食物过敏中脂质代谢物水平改变。

Metabolomic profiling revealed altered lipid metabolite levels in childhood food allergy.

机构信息

Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea.

Department of Pediatrics, Gangnam Severance Hospital, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.

出版信息

J Allergy Clin Immunol. 2022 May;149(5):1722-1731.e9. doi: 10.1016/j.jaci.2021.10.034. Epub 2021 Nov 26.

DOI:10.1016/j.jaci.2021.10.034
PMID:34843802
Abstract

BACKGROUND

The pathophysiology of childhood food allergy (FA) and its natural history are poorly understood. Clarification of the underlying mechanism may help identify novel biomarkers and strategies for clinical intervention in children with FA.

OBJECTIVE

This study aimed to identify metabolites associated with the development and resolution of FA.

METHODS

The metabolomic profiles of 20 children with FA and 20 healthy controls were assessed by liquid chromatography-tandem mass spectrometry. Comparative analysis was performed to identify metabolites associated with FA and FA resolution. For subjects with FA, serum samples were collected at the time of diagnosis and after resolution to identify the changes in metabolite levels. The selected metabolites were then quantified in a quantification cohort to validate the results. Finally, genome-wide association analysis of the metabolite levels was performed.

RESULTS

The study demonstrated a significantly higher level of sphingolipid metabolites and a lower level of acylcarnitine metabolites in children with FA than those in healthy controls. At diagnosis, subjects with resolving FA had a significantly high level of omega-3 metabolites and a low level of platelet-activating factors compared to persistent FA. However, the level of omega-3 metabolites decreased in children with resolving FA but increased in children with persistent FA during the same time. The quantification data of omega-3-derived resolvins, platelet-activating factor, and platelet-activating factor acetylhydrolase activity further supported these results.

CONCLUSION

The lipid metabolite profile is closely related to childhood FA and FA resolution. This study suggests potential predictive biomarkers and provides insight into the mechanisms underlying childhood FA.

摘要

背景

儿童食物过敏(FA)的病理生理学及其自然史尚未被充分了解。阐明潜在机制可能有助于发现新的生物标志物,并为儿童 FA 的临床干预提供策略。

目的

本研究旨在鉴定与 FA 的发生和缓解相关的代谢物。

方法

通过液相色谱-串联质谱法对 20 名 FA 患儿和 20 名健康对照者的代谢组学图谱进行评估。通过比较分析鉴定与 FA 和 FA 缓解相关的代谢物。对于 FA 患儿,在诊断时和缓解后采集血清样本,以鉴定代谢物水平的变化。然后在定量队列中对选定的代谢物进行定量,以验证结果。最后,对代谢物水平进行全基因组关联分析。

结果

本研究表明,与健康对照组相比,FA 患儿的鞘脂类代谢物水平显著升高,酰基辅酶 A 代谢物水平显著降低。在诊断时,与持续 FA 相比,缓解 FA 的患儿体内 ω-3 代谢物水平显著升高,血小板激活因子水平显著降低。然而,在同一时期内,缓解 FA 的患儿体内 ω-3 代谢物水平降低,但持续 FA 的患儿体内 ω-3 代谢物水平升高。ω-3 衍生的 resolvins、血小板激活因子和血小板激活因子乙酰水解酶活性的定量数据进一步支持了这些结果。

结论

脂质代谢物谱与儿童 FA 和 FA 缓解密切相关。本研究提示了潜在的预测生物标志物,并为儿童 FA 的发病机制提供了新的见解。

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