title: A novel lipidomic strategy reveals plasma phospholipid signatures associated with respiratory disease severity in cystic fibrosis patients.
abstract: The aim of this study was to search for lipid signatures in blood plasma from cystic fibrosis (CF) patients using a novel MALDI-TOF-ClinProTools strategy, initially developed for protein analysis, and thin layer chromatography coupled to MALDI-TOF (TLC-MALDI). Samples from 33 CF patients and 18 healthy children were subjected to organic extraction and column chromatography separation of lipid classes. Extracts were analyzed by MALDI-TOF, ion signatures were compared by the ClinProTools software and by parallel statistical analyses. Relevant peaks were identified by LC-MSn. The ensemble of analyses provided 11 and 4 peaks differentially displayed in CF vs healthy and in mild vs severe patients respectively. Ten ions were significantly decreased in all patients, corresponding to 4 lysophosphatidylcholine (18:0, 18:2, 20:3, and 20:5) and 6 phosphatidylcholine (36:5, O-38:0, 38:4, 38:5, 38:6, and P-40:1) species. One sphingolipid, SM(d18:0), was significantly increased in all patients. Four PC forms (36:3, 36:5, 38:5, and 38:6) were consistently downregulated in severe vs mild patients. These observations were confirmed by TLC-MALDI. These results suggest that plasma phospholipid signatures may be able to discriminate mild and severe forms of CF, and show for the first time MALDI-TOF-ClinProTools as a suitable methodology for the search of lipid markers in CF.
authors.affiliation: Plateau Proteome Necker, Université Paris Descartes, IFR94, Paris, France.
authors.forename: Ida Chiara
authors.initials: IC
authors.lastname: Guerrera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.forename: Dorota
authors.initials: D
authors.lastname: Sands
authors.forename: Anna
authors.initials: A
authors.lastname: Nowakowska
authors.forename: Julien
authors.initials: J
authors.lastname: Colas
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sermet-Gaudelus
authors.forename: Martin
authors.initials: M
authors.lastname: Schuerenberg
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.forename: Aleksander
authors.initials: A
authors.lastname: Edelman
authors.forename: Mario
authors.initials: M
authors.lastname: Ollero
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002855:Chromatography, Thin Layer / Q000379:methods; D003550:Cystic Fibrosis / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007223:Infant; D008055:Lipids / Q000737:chemistry*; D008244:Lysophosphatidylcholines / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D010743:Phospholipids / Q000097:blood*; D012120:Respiration Disorders / Q000097:blood* / Q000175:diagnosis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008055:Lipids; D008244:Lysophosphatidylcholines; D010743:Phospholipids