Distinctive metabolic profiles between Cystic Fibrosis mutational subclasses and lung function.

Area of Science:

• Biochemistry
• Genetics
• Metabolomics

Background:

• Cystic fibrosis (CF) is a severe monogenic disease caused by CFTR mutations.
• Mutations lead to CFTR protein defects, varying clinical presentations, and disease severity.
• Understanding CF's metabolic alterations is crucial for diagnosis and treatment.

Purpose of the Study:

• To establish a comprehensive metabolomic profile in CF patients.
• To analyze metabolic differences across CF mutation classes and in relation to lung function.

Main Methods:

• Utilized chemical isotope labeling liquid chromatography-mass spectrometry metabolomics.
• Analyzed serum metabolic profiles of 39 CF patients (young and adult) and 30 healthy controls.
• Compared CF patients vs. controls, different CF mutational classes, and CF classes III vs. IV, correlating with lung function (FEV1%).

Main Results:

• Identified 78, 20, and 13 significantly dysregulated metabolites in CF vs. controls, among classes, and between classes III/IV, respectively.
• Key altered metabolites include amino acids, di-/tri-peptides, glutathione, glutamine, glutamate, and arginine.
• Lung function (FEV1%) correlated with decreased glutamic acid and increased guanosine.

Conclusions:

• Metabolomic profiling reveals significant alterations in amino acids and dipeptides, impacting glutathione metabolism in CF.
• Two metabolites, 3,4-dihydroxymandelate-3-O-sulfate and 5-Aminopentanoic acid, were consistently identified and may be sensitive CF biomarkers.