Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury

Shui Q. Ye, Brett A. Simon, James P. Maloney, April Zambelli-Weiner, Li Gao, Audrey Grant, R. Blaine Easley, Bryan J. McVerry, Rubin M. Tuder, Theodore Standiford, Roy G. Brower, Kathleen C. Barnes, Joe G.N. Garcia

Research output: Contribution to journalArticle

294 Scopus citations

Abstract

Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease.

Original languageEnglish (US)
Pages (from-to)361-370
Number of pages10
JournalAmerican journal of respiratory and critical care medicine
Volume171
Issue number4
DOIs
StatePublished - Feb 15 2005
Externally publishedYes

Keywords

  • Gene expression
  • Lung disease
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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  • Cite this

    Ye, S. Q., Simon, B. A., Maloney, J. P., Zambelli-Weiner, A., Gao, L., Grant, A., Easley, R. B., McVerry, B. J., Tuder, R. M., Standiford, T., Brower, R. G., Barnes, K. C., & Garcia, J. G. N. (2005). Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. American journal of respiratory and critical care medicine, 171(4), 361-370. https://doi.org/10.1164/rccm.200404-563OC