Biomarkers for cystic fibrosis lung disease: Application of SELDI-TOF mass spectrometry to BAL fluid

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• 作者：Gordon MacGregor ; Robert D. Gray ; Thomas N. Hilliard ; Margaret Imrie ; A. Christopher Boyd ; Eric W.F.W. Alton ; Andrew Bush ; Jane C. Davies ; J. Alastair Innes ; David J. Porteous ; Andrew P. Greening
• 关键词：Paediatric ; Proteomics ; Pulmonary disease ; Bronchoscopy
• 刊名：Journal of Cystic Fibrosis
• 出版年：2008
• 出版时间：September 2008
• 年：2008
• 卷：7
• 期：5
• 页码：352-358
• 全文大小：652 K

文摘

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.