Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant recipients
Background: Obliterative bronchiolitis poses a primary obstacle for long-term survival of lung transplant recipients and manifests clinically as bronchiolitis obliterans syndrome (BOS). Establishing a molecular level screening method to detect BOS-related proteome changes before its diagnosis by for...
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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
August 27, 2011
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| In: |
Transplantation
Year: 2011, Jahrgang: 92, Heft: 4, Pages: 477-485 |
| ISSN: | 1534-6080 |
| DOI: | 10.1097/TP.0b013e318224c109 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/TP.0b013e318224c109 Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/transplantjournal/Fulltext/2011/08270/Proteomic_Bronchiolitis_Obliterans_Syndrome_Risk.15.aspx 
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| Verfasserangaben: | Thomas Wolf, Tonio Oumeraci, Jens Gottlieb, Andreas Pich, Benedikt Brors, Roland Eils, Axel Haverich, Brigitte Schlegelberger, Tobias Welte, Marc Zapatka, and Nils von Neuhoff |
MARC
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| 520 | |a Background: Obliterative bronchiolitis poses a primary obstacle for long-term survival of lung transplant recipients and manifests clinically as bronchiolitis obliterans syndrome (BOS). Establishing a molecular level screening method to detect BOS-related proteome changes before its diagnosis by forced expiratory volume surrogate marker criteria was the main objective of this study. - Methods: Bronchoalveolar lavage was performed in 82 lung transplant recipients (48/34 with/without known BOS development) at different time points between 12 and 48 months after lung transplantation. A mass spectrometry-based method was devised to generate bronchoalveolar lavage fluid proteome profiles that were screened for BOS-specific alterations. Statistically significant marker peptides and proteins were identified and validated by in-gel digestion, tandem mass spectrometric sequencing, and quantitative immunoassays. - Results: Among the panel of statistically significant markers were Clara cell protein, calgranulin A, human neutrophil peptides, and the antimicrobial agent histatin. To assess their clinical relevance, a highly sensitive and specific classifier model was developed. Positive BOS classification by monitoring of seven polypeptides correlated strongly with a significant decrease in BOS-free time. Thus, it was possible to detect high-risk patients early on in the pathogenetic process. - Conclusions: Monitoring the bronchoalveolar lavage fluid levels of seven polypeptides detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows a reliable prediction of early BOS using a Random Forest decision tree-based classifier model. The high accuracy of this robust model and its synergistic potential in combination with established forced expiratory volume-based diagnostics could make it an effective tool to supplement the current diagnostic regime after multicentric validation. | ||
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