Proteomic Bronchiolitis Obliterans Syndrome Risk Monitoring in Lung Transplant Recipients

Wolf, Thomas; Oumeraci, Tonio; Gottlieb, Jens; Pich, Andreas; Brors, Benedikt; Eils, Roland; Haverich, Axel; Schlegelberger, Brigitte; Welte, Tobias; Zapatka, Marc; Neuhoff, Nils von

doi:10.1097/tp.0b013e318224c109

Cited by 15 publications

(10 citation statements)

References 44 publications

(42 reference statements)

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“…All of these groups, however, had higher BAL CCSP levels than those in BOS. This suggests that CCSP, while reduced in BOS, may be less useful as a biomarker for early disease identification, in contrast to the preliminary results observed in the prior studies (10–13). In part, these results might reflect the primarily cross‐sectional nature of our study (15).…”

Section: Discussioncontrasting

confidence: 78%

“…Due to the pilot nature of that study, however, confirmation of the proteins identified in the MALDI‐TOF profile was not performed. More recently, Wolf and colleagues generated BAL proteome profiles for 82 lung transplant recipients, 48 of whom developed BOS (12). Among the panel of significant markers was CCSP; however, this finding was validated by ELISA in only 13 patients, 8 of whom had BOS.…”

Section: Discussionmentioning

confidence: 99%

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Epithelial Clara Cell Injury Occurs in Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

Kelly

Kennedy

Jain

et al. 2012

American Journal of Transplantation

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Bronchiolitis obliterans syndrome (BOS) is a condition of progressive airflow obstruction that affects a majority of lung transplant recipients and limits long-term post-transplant survival. Although epithelial injury appears central to the development of BOS, little is known regarding the specific epithelial cell types that are affected in this condition. We hypothesized that BOS would involve preferential injury to the secretory Clara cells that function in innate defense and epithelial repair. To test this hypothesis, we assessed tissue transcript, tissue protein, and lung fluid protein expression of Clara cell secretory protein (CCSP), a marker for Clara cells, in lung transplant recipients with BOS, BOS-free patients, and in donor controls. Our results demonstrate that CCSP tissue transcript and protein expression are significantly reduced in lung transplant recipients with BOS as compared to BOS-free or donor controls. In addition, we demonstrate that CCSP protein levels are significantly reduced in the lung fluid of patients with BOS as compared to BOS-free controls, in cross-sectional and longitudinal analysis. Collectively, these complementary results illustrate that BOS involves a selective alteration in the distribution and function of bronchiolar Clara cells.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Epithelial Clara Cell Injury Occurs in Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

Kelly

Kennedy

Jain

et al. 2012

American Journal of Transplantation

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“…Peroxiredoxin II was found to be exclusively expressed in BOS, whereas surfactant protein A displayed significantly lower expression in BOS patients compared to stable controls [70]. Based on a panel of seven statistically significant polypeptide markers, Wolf et al established a predictor model to detect BOS-related proteome changes in BALF before its clinical diagnosis [71]. …”

Section: Lung Transplantationmentioning

confidence: 98%

Proteomics in Transplantation

Kienzl-Wagner

Brandacher

2014

Advances in Clinical Chemistry

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“…Treatment is limited to immunosuppressant augmentation to which response is poor and five-year survival after diagnosis is only 30-40% [2]. While single proteins, such as human neutrophil defensin, MMP-9, surfactant protein A, and unique peptides have previously been identified that correlate with the development of BOS, the global longitudinal changes in proteins and their associated biological processes in the development of BOS have not been described [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal protein expression patterns in bronchiolitis obliterans syndrome

Roark¹,

Sandri²,

Dey³

et al. 2015

Pulmonol Respir Res

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Background: Lung transplant is an effective therapy, however, long-term survival is currently limited due to the high rate of bronchiolitis obliterans syndrome (BOS). The longitudinal biological changes that occur as a patient progresses to BOS are not well understood. The objective of this study was to evaluate the bronchoalveolar lavage fluid (BALF) proteome, seeking to identify proteins and their representative biological functions that have coherent changes in the development of BOS. Methods: Isobaric tag for relative and absolute quantification(iTRAQ ® ) with LC MS/MS were performed on BALF enriched for medium and low abundance proteins from three time points (range 699 days pre-BOS to 83 days post-BOS) taken from four patients that developed BOS. Controls consisted of pooled samples from nine patients who did not develop BOS within five years of sample acquisition. We investigated how the protein profiles changed longitudinally as the patient progressed towards BOS using Short Time-series Expression Miner, (STEM), analysis and identified gene ontology terms associated with these protein clusters. Results: We identified 871 unique proteins at a 5% FDR. STEM analysis revealed three models that met statistical significance.Gene ontology revealed three biological processes that associated with these models and included: sequestering of actin monomers, cytoskeletal organization and an inflammatory or defense response. Conclusion: Longitudinal and gene cluster models reveal coherent changes in BALF proteins as patients approach BOS.

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Proteomic Bronchiolitis Obliterans Syndrome Risk Monitoring in Lung Transplant Recipients

Cited by 15 publications

References 44 publications

Epithelial Clara Cell Injury Occurs in Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

Epithelial Clara Cell Injury Occurs in Bronchiolitis Obliterans Syndrome After Human Lung Transplantation

Proteomics in Transplantation

Longitudinal protein expression patterns in bronchiolitis obliterans syndrome

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