Biomarkers for cystic fibrosis lung disease: application of SELDI-TOF mass spectrometry to BAL fluid.
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.
MacGregor
Gordon
G
School of Molecular and Clinical Medicine, University of Edinburgh, EH4 2XU, United Kingdom.
Gray
Robert D
RD
Hilliard
Thomas N
TN
Imrie
Margaret
M
Boyd
A Christopher
AC
Alton
Eric W F W
EW
Bush
Andrew
A
Davies
Jane C
JC
Innes
J Alastair
JA
Porteous
David J
DJ
Greening
Andrew P
AP
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
D015415:Biomarkers