title: Biomarkers for cystic fibrosis lung disease: application of SELDI-TOF mass spectrometry to BAL fluid.
abstract: BACKGROUND
  For cystic fibrosis (CF) patients there is a lack of good assays of disease activity and response to new therapeutic interventions, including gene therapy. Current measures of airways inflammation severity are insensitive or non-specific.
  
  
  METHODS
  Bronchoalveolar lavage fluid from 39 CF children and 38 respiratory disease controls was obtained at bronchoscopy and analysed by surface enhanced laser desorption ionisation time of flight (SELDI-TOF) mass spectrometry. Recognized proteins were assessed for CF disease specificity. Individual protein identification of specific peaks was performed.
  
  
  RESULTS
  1277 proteins/peptides, >4 kDa, were detected using 12 different surfaces and binding conditions. 202 proteins/peptides were differentially expressed in the CF samples (p<0.001), 167 up-regulated and 35 down-regulated. The most discriminatory biomarker had a mass of 5.163 kDa. The most abundant, with a mass of 10.6 kDa, was identified as s100 A8 (calgranulin A).
  
  
  CONCLUSIONS
  The application of SELDI-TOF mass spectrometry allows evaluation of proteins in BAL fluid avoiding the limitations of only analysing predetermined proteins and potentially identifying proteins not previously appreciated as biomarkers. Its application to cystic fibrosis should enable appropriate evaluation of evolving illness, of gene therapy and other new therapies.
authors.affiliation: School of Molecular and Clinical Medicine, University of Edinburgh, EH4 2XU, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: MacGregor
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gray
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Hilliard
authors.forename: Margaret
authors.initials: M
authors.lastname: Imrie
authors.forename: A Christopher
authors.initials: AC
authors.lastname: Boyd
authors.forename: Eric W F W
authors.initials: EW
authors.lastname: Alton
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
authors.forename: J Alastair
authors.initials: JA
authors.lastname: Innes
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Greening
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D001999:Bronchoscopy; D016022:Case-Control Studies; D002648:Child; D003550:Cystic Fibrosis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers