Introduction

Cystic fibrosis (CF) is a lethal multisystemic disease of a monogenic origin with numerous mutations. Functional defects in the cystic fibrosis transmembrane conductance receptor (CFTR) protein based on these mutations are categorised into distinct classes having different clinical presentations and disease severity.

Objectives

The present study aimed to create a comprehensive metabolomic profile of altered metabolites in patients with CF, among different classes and in relation to lung function.

Methods

A chemical isotope labeling liquid chromatography-mass spectrometry metabolomics was used to study the serum metabolic profiles of young and adult CF (n = 39) patients and healthy controls (n = 30). Comparisons were made at three levels, CF vs. controls, among mutational classes of CF, between CF class III and IV, and correlated the lung function findings.

Results

A distinctive metabolic profile was observed in the three analyses. 78, 20, and 13 significantly differentially dysregulated metabolites were identified in the patients with CF, among the different classes and between class III and IV, respectively. The significantly identified metabolites included amino acids, di-, and tri-peptides, glutathione, glutamine, glutamate, and arginine metabolism. The top significant metabolites include 1-Aminopropan-2-ol, ophthalmate, serotonin, cystathionine, and gamma-glutamylglutamic acid. Lung function represented by an above-average FEV1% level was associated with decreased glutamic acid and increased guanosine levels.

Conclusion

Metabolomic profiling identified alterations in different amino acids and dipeptides, involved in regulating glutathione metabolism. Two metabolites, 3,4-dihydroxymandelate-3-O-sulfate and 5-Aminopentanoic acid, were identified in common between the three anlayses and may represent as highly sensitive biomarkers for CF.

中文翻译：

---

囊性纤维化突变亚类与肺功能之间的独特代谢特征

介绍

囊性纤维化 (CF) 是一种致命的多系统疾病，具有多种突变的单基因起源。基于这些突变的囊性纤维化跨膜传导受体 (CFTR) 蛋白的功能缺陷被分为不同的类别，具有不同的临床表现和疾病严重程度。

目标

本研究旨在建立 CF 患者不同类别和与肺功能相关的改变代谢物的综合代谢组学特征。

方法

化学同位素标记液相色谱-质谱代谢组学用于研究年轻和成人 CF (n = 39) 患者和健康对照 (n = 30) 的血清代谢特征。在三个水平上进行比较，CF 与对照，CF 的突变类别之间，CF 类别 III 和 IV 之间，并关联肺功能发现。

结果

在三个分析中观察到独特的代谢特征。在 CF 患者中，分别在不同类别中以及在 III 类和 IV 类之间鉴定出 78、20 和 13 种显着差异失调的代谢物。显着鉴定的代谢物包括氨基酸、二肽和三肽、谷胱甘肽、谷氨酰胺、谷氨酸和精氨酸代谢。最重要的代谢物包括 1-Aminopropan-2-ol、眼酸盐、血清素、胱硫醚和 γ-谷氨酰谷氨酸。以高于平均水平的 FEV1% 水平为代表的肺功能与谷氨酸减少和鸟苷水平增加有关。

结论

代谢组学分析确定了不同氨基酸和二肽的改变，参与调节谷胱甘肽代谢。两种代谢物，3,4-dihydroxymandelate-3-O-sulfate 和 5-Aminopentanoic 酸，在三种分析之间被鉴定出，可能代表 CF 的高度敏感生物标志物。