Proteomic Characterization Reveals That MMP‐3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation |
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| 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 |
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| Affiliation: | 1. Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN;2. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN;3. Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN;4. Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN;5. Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN;6. Proteomics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA;7. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;8. Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan;9. Pulmonary Division, Indiana University School of Medicine, Indianapolis, IN;10. University of Washington School of Medicine, Seattle, WA |
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| 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. |
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| Keywords: | translational research/science basic (laboratory) research/science bone marrow/hematopoietic stem cell transplantation lung transplantation/pulmonology biomarker bronchiolitis obliterans (BOS) |
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