It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis
Background: The obstructive phenotype of chronic lung allograft dysfunction, bronchiolitis obliterans syndrome (BOS), is diagnosed after lung transplantation (LTx) when irreversible airway obstruction is already present. This study aimed to investigate biomarkers indicative of aberrant repair result...
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Elsevier
2025-08-01
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| Series: | JHLT Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950133425000989 |
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| author | Eline A. van der Ploeg Alen Faiz Greta J. Teitsma Alejandro Sánchez Brotons Natalia Govorukhina Jannie M.B. Sand Diana J. Leeming Barbro N. Melgert Peter Horvatovich Janette K. Burgess C. Tji Gan |
| author_facet | Eline A. van der Ploeg Alen Faiz Greta J. Teitsma Alejandro Sánchez Brotons Natalia Govorukhina Jannie M.B. Sand Diana J. Leeming Barbro N. Melgert Peter Horvatovich Janette K. Burgess C. Tji Gan |
| author_sort | Eline A. van der Ploeg |
| collection | DOAJ |
| description | Background: The obstructive phenotype of chronic lung allograft dysfunction, bronchiolitis obliterans syndrome (BOS), is diagnosed after lung transplantation (LTx) when irreversible airway obstruction is already present. This study aimed to investigate biomarkers indicative of aberrant repair resulting in a fibrotic response and inflammation signals in the serum of patients with BOS. Methods: LTx patients transplanted at the University Medical Center Groningen between 2004 and 2017 were screened. Nineteen patients with BOS were selected and matched with 19 patients with non-BOS. Only patients for whom lung function and longitudinal serum samples post-LTx were available were included. Enzyme-linked immunosorbent assays were performed for neoepitopes of collagen types I, III, and VI and osteoprotegerin (OPG) in serum. Additionally, serum samples were analyzed by label-free liquid chromatography with tandem mass spectrometry proteomics analysis. Results: Collagen neoepitopes did not differ significantly between patients with BOS and non-BOS at any timepoint. OPG was significantly higher in non-BOS compared to BOS 6 months before BOS onset (p < 0.04). In proteomics analysis, proteins indicating cell repair and proliferation, namely human type II keratin-6 and centromere protein F (both FDR < 0.1), were significantly lower 3 months before BOS onset in patients with BOS compared to patients with non-BOS. C-reactive protein (FDR < 0.05) and SERPINA3 (FDR < 0.05), among others, were higher in end-stage patients with BOS compared to patients with non-BOS. Conclusions: Differences in the expression of proteins that reflect the complex interplay between aberrant repair and inflammation in BOS were identified. These proteins should be investigated and validated in larger cohorts and may aid in expanding knowledge about the development of BOS. |
| format | Article |
| id | doaj-art-87eac4b6cfea426c8a66274bdebd2b95 |
| institution | DOAJ |
| issn | 2950-1334 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| series | JHLT Open |
| spelling | doaj-art-87eac4b6cfea426c8a66274bdebd2b952025-08-20T03:02:59ZengElsevierJHLT Open2950-13342025-08-01910030310.1016/j.jhlto.2025.100303It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysisEline A. van der Ploeg0Alen Faiz1Greta J. Teitsma2Alejandro Sánchez Brotons3Natalia Govorukhina4Jannie M.B. Sand5Diana J. Leeming6Barbro N. Melgert7Peter Horvatovich8Janette K. Burgess9C. Tji Gan10Department of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Corresponding author: Eline A. van der Ploeg, University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine, Postbox 30.001, 9700 RB Groningen, the Netherlands.Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences, University of Technology Sydney, Sydney, Australia; Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the NetherlandsDepartment of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the NetherlandsHepatic and Pulmonary Research, Nordic Bioscience, Herlev, DenmarkHepatic and Pulmonary Research, Nordic Bioscience, Herlev, DenmarkGroningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the NetherlandsDepartment of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the NetherlandsGroningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Pulmonary Medicine, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsBackground: The obstructive phenotype of chronic lung allograft dysfunction, bronchiolitis obliterans syndrome (BOS), is diagnosed after lung transplantation (LTx) when irreversible airway obstruction is already present. This study aimed to investigate biomarkers indicative of aberrant repair resulting in a fibrotic response and inflammation signals in the serum of patients with BOS. Methods: LTx patients transplanted at the University Medical Center Groningen between 2004 and 2017 were screened. Nineteen patients with BOS were selected and matched with 19 patients with non-BOS. Only patients for whom lung function and longitudinal serum samples post-LTx were available were included. Enzyme-linked immunosorbent assays were performed for neoepitopes of collagen types I, III, and VI and osteoprotegerin (OPG) in serum. Additionally, serum samples were analyzed by label-free liquid chromatography with tandem mass spectrometry proteomics analysis. Results: Collagen neoepitopes did not differ significantly between patients with BOS and non-BOS at any timepoint. OPG was significantly higher in non-BOS compared to BOS 6 months before BOS onset (p < 0.04). In proteomics analysis, proteins indicating cell repair and proliferation, namely human type II keratin-6 and centromere protein F (both FDR < 0.1), were significantly lower 3 months before BOS onset in patients with BOS compared to patients with non-BOS. C-reactive protein (FDR < 0.05) and SERPINA3 (FDR < 0.05), among others, were higher in end-stage patients with BOS compared to patients with non-BOS. Conclusions: Differences in the expression of proteins that reflect the complex interplay between aberrant repair and inflammation in BOS were identified. These proteins should be investigated and validated in larger cohorts and may aid in expanding knowledge about the development of BOS.http://www.sciencedirect.com/science/article/pii/S2950133425000989bronchiolitis obliterans syndromechronic lung allograft dysfunctionlung transplantationfibrosisinflammation |
| spellingShingle | Eline A. van der Ploeg Alen Faiz Greta J. Teitsma Alejandro Sánchez Brotons Natalia Govorukhina Jannie M.B. Sand Diana J. Leeming Barbro N. Melgert Peter Horvatovich Janette K. Burgess C. Tji Gan It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis JHLT Open bronchiolitis obliterans syndrome chronic lung allograft dysfunction lung transplantation fibrosis inflammation |
| title | It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis |
| title_full | It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis |
| title_fullStr | It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis |
| title_full_unstemmed | It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis |
| title_short | It takes two: Aberrant repair and low-grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis |
| title_sort | it takes two aberrant repair and low grade inflammation characterize bronchiolitis obliterans syndrome after lung transplantation in serum proteomic analysis |
| topic | bronchiolitis obliterans syndrome chronic lung allograft dysfunction lung transplantation fibrosis inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2950133425000989 |
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