Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant recipients

• Verfasst von: Wolf, Thomas [VerfasserIn]
• Verfasst von: Oumeraci, Tonio [VerfasserIn]
• Verfasst von: Gottlieb, Jens [VerfasserIn]
• Verfasst von: Pich, Andreas [VerfasserIn]
• Verfasst von: Brors, Benedikt [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Verfasst von: Haverich, Axel [VerfasserIn]
• Verfasst von: Schlegelberger, Brigitte [VerfasserIn]
• Verfasst von: Welte, Tobias [VerfasserIn]
• Verfasst von: Zapatka, Marc [VerfasserIn]
• Verfasst von: von Neuhoff, Nils [VerfasserIn]
• Titel: Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant recipients
• Verf.angabe: Thomas Wolf, Tonio Oumeraci, Jens Gottlieb, Andreas Pich, Benedikt Brors, Roland Eils, Axel Haverich, Brigitte Schlegelberger, Tobias Welte, Marc Zapatka, and Nils von Neuhoff
• E-Jahr: 2011
• Jahr: August 27, 2011
• Umfang: 9 S.
• Fussnoten: Gesehen am 24.11.2022
• Titel Quelle: Enthalten in: Transplantation
• Ort Quelle: Hagerstown, Md. : Lippincott Williams & Wilkins, 1963
• Jahr Quelle: 2011
• Band/Heft Quelle: 92(2011), 4, Seite 477-485
• ISSN Quelle: 1534-6080
• DOI: doi:10.1097/TP.0b013e318224c109
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1823547737

Abstract

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.