Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation

X. Liu, Z. Yue, J. Yu, E. Daguindau, K. Kushekhar, Q. Zhang, Y. Ogata, P. R. Gafken, Y. Inamoto, A. Gracon, D. S. Wilkes, J. A. Hansen, S. J. Lee, J. Y. Chen, S. Paczesny

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For protein candidate discovery, we compared plasma pools from HCT transplantation recipients with BOS at onset (n = 12), pulmonary infection (n = 16), chronic graft-versus-host disease without pulmonary involvement (n = 15) and no chronic complications after HCT (n = 15). Pools were labeled with different tags (isobaric tags for relative and absolute quantification), and two software tools identified differentially expressed proteins (≥1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase 3 (MMP3), was evaluated by enzyme-linked immunosorbent assay in plasma of a verification cohort (n = 112) with and without BOS following HCT (n = 76) or lung transplantation (n = 36). MMP3 plasma concentrations differed significantly between patients with and without BOS (area under the receiver operating characteristic curve 0.77). Consequently, MMP3 represents a potential noninvasive blood test for diagnosis of BOS.

Original languageEnglish (US)
Pages (from-to)2342-2351
Number of pages10
JournalAmerican Journal of Transplantation
Volume16
Issue number8
DOIs
StatePublished - Aug 1 2016

Keywords

  • basic (laboratory) research/science
  • biomarker
  • bone marrow/hematopoietic stem cell transplantation
  • bronchiolitis obliterans (BOS)
  • lung transplantation/pulmonology
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Liu, X., Yue, Z., Yu, J., Daguindau, E., Kushekhar, K., Zhang, Q., Ogata, Y., Gafken, P. R., Inamoto, Y., Gracon, A., Wilkes, D. S., Hansen, J. A., Lee, S. J., Chen, J. Y., & Paczesny, S. (2016). Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation. American Journal of Transplantation, 16(8), 2342-2351. https://doi.org/10.1111/ajt.13750