Proteomic identification of human neutrophil alpha-defesins in chronic lung allograft rejection

Gary L. Nelsestuen, Michael B. Martinez, Marshall I. Hertz, Kay Savik, Christine H. Wendt

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Chronic allograft rejection remains a leading cause of morbidity and mortality in lung transplant recipients. Currently, diagnosis is based on lung biopsies or the presence of bronchiolitis obliterans syndrome (BOS). To identify a biomarker of rejection we performed a proteome survey of archived bronchoalveolar lavage fluid (BALF) acquired from lung transplant recipients between 1993 and 1996 using mass spectrometry (MS). A total of 126 BALF samples from 57 individuals were tested. Initial MS assessment revealed numerous differences in a majority of individuals who experienced BOS, but three unusually intense peaks at m/z = 3373, 3444, and 3488. These were identified as human neutrophil peptides 1-3 (HNP). Quantification by enzyme-linked immunoabsorbent assay showed an elevated HNP level (>0.3 ng/μg protein) in 89% of patients who developed BOS2-3 within 15 months, reaching as high as 6% of the total BALF protein. In control patients, 35% demonstrated a slightly elevated HNP level that declined in all who had subsequent BALF available for testing. HNP levels did not correlate with episodes of acute rejection, cytomegalovirus or fungal infection. In conclusion, elevated HNP levels are associated with the onset of BOS and can predate the clinical onset of disease up to 15 months.

Original languageEnglish (US)
Pages (from-to)1705-1713
Number of pages9
JournalProteomics
Volume5
Issue number6
DOIs
StatePublished - Apr 2005

Keywords

  • Biomarker
  • Chronic lung allograft rejection
  • Human neutrophil defensins
  • Matrix-assisted laser desorption/ionization-time of flight protein profile

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