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

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.

• Authors: 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
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 16 Issue 8 Pg. 2342-51 (08 2016) ISSN: 1600-6143 [Electronic] United States
• PMID: 26887344 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Biomarkers
• Proteome
• MMP3 protein, human
• Matrix Metalloproteinase 3

Topics

• Adult
• Aged
• Biomarkers (blood)
• Bronchiolitis Obliterans (blood, diagnosis, etiology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Follow-Up Studies
• Graft vs Host Disease (blood, diagnosis, etiology)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Lung Transplantation (adverse effects)
• Male
• Matrix Metalloproteinase 3 (blood)
• Middle Aged
• Prognosis
• Proteome (analysis)
• Proteomics (methods)
• Transplantation, Homologous
• Young Adult