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Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant recipients.

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.

journal_name

Transplantation

journal_title

Transplantation

authors

Wolf T,Oumeraci T,Gottlieb J,Pich A,Brors B,Eils R,Haverich A,Schlegelberger B,Welte T,Zapatka M,von Neuhoff N

doi

10.1097/TP.0b013e318224c109

subject

Has Abstract

pub_date

2011-08-27 00:00:00

pages

477-85

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

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Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant recipients.