Lipidome Alterations Induced by Cystic Fibrosis, CFTR Mutation, and Lung Function

Cystic fibrosis is a genetic pathology
characterized by abnormal
accumulation of mucus in the respiratory, gastrointestinal, and reproductive
tracts, caused by mutations in the CFTR gene. Although
the classical presentation of the condition is well known, there is
still a need for a better characterization of metabolic alterations
related to cystic fibrosis and different genotypic mutations. We employed
untargeted, comprehensive lipidomics of blood serum samples to investigate
alterations in the lipid metabolism related to the pathology, mutation
classes, and lung function decline. Six unique biomarker candidates
were able to independently differentiate diseased individuals from
healthy controls with excellent performance. Cystic fibrosis patients
showed dyslipidemia for most lipid subclasses, with significantly
elevated odd-chain and polyunsaturated fatty acyl lipids. Phosphatidic
acids and diacylglycerols were particularly affected by different
genotypic mutation classes. We selected a biomarker panel composed
of four lipids, including two ceramides, one sphingomyelin, and one
fatty acid, which correctly classified all validation samples from
classes III and IV. A biomarker panel of five oxidized lipids was
further selected to differentiate patients with reduced lung function,
measured as predicted FEV1%. Our results indicate that cystic fibrosis
is deeply related to lipid metabolism and provide new clues for the
investigation of the disease mechanisms and therapeutic targets.