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Corticotropin releasing hormone as an identifier of bronchiolitis obliterans syndrome

Niroomand, Anna LU ; Ghaidan, Haider LU orcid ; Hallgren, Oskar LU ; Hansson, Lennart LU ; Larsson, Hillevi LU ; Wagner, Darcy LU orcid ; Mackova, Martina ; Halloran, Kieran ; Hyllén, Snejana LU and Lindstedt, Sandra LU (2022) In Scientific Reports 12. p.1-11
Abstract

Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1-3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR.... (More)

Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1-3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR. Samples were collected at baseline and 1-year post transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to validate the findings of the PEA analysis across both time points and microarray datasets from other lung transplantation centers demonstrated the same findings. Significant decreases in the plasma protein levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 and an increase in MMP-9 and CTSL1 were seen in patients who developed BOS compared to those who did not. In this study, CRH is presented as a novel potential biomarker in the progression of disease because of its decreased levels in patients across all BOS grades. Additionally, biomarkers involving the remodeling of the extracellular matrix (ECM), such as MMP-9 and CTSL1, were increased in BOS patients.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Bronchiolitis Obliterans/etiology, Corticotropin-Releasing Hormone, Graft Rejection/diagnosis, Humans, Lung Transplantation/adverse effects, Matrix Metalloproteinase 9, Syndrome
in
Scientific Reports
volume
12
article number
8413
pages
1 - 11
publisher
Nature Publishing Group
external identifiers
  • scopus:85130358775
  • pmid:35589861
ISSN
2045-2322
DOI
10.1038/s41598-022-12546-1
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
06e1c652-e342-4c8f-95ea-7f58cb74a325
date added to LUP
2022-05-30 20:37:07
date last changed
2024-06-12 16:42:33
@article{06e1c652-e342-4c8f-95ea-7f58cb74a325,
  abstract     = {{<p>Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1-3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR. Samples were collected at baseline and 1-year post transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to validate the findings of the PEA analysis across both time points and microarray datasets from other lung transplantation centers demonstrated the same findings. Significant decreases in the plasma protein levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 and an increase in MMP-9 and CTSL1 were seen in patients who developed BOS compared to those who did not. In this study, CRH is presented as a novel potential biomarker in the progression of disease because of its decreased levels in patients across all BOS grades. Additionally, biomarkers involving the remodeling of the extracellular matrix (ECM), such as MMP-9 and CTSL1, were increased in BOS patients.</p>}},
  author       = {{Niroomand, Anna and Ghaidan, Haider and Hallgren, Oskar and Hansson, Lennart and Larsson, Hillevi and Wagner, Darcy and Mackova, Martina and Halloran, Kieran and Hyllén, Snejana and Lindstedt, Sandra}},
  issn         = {{2045-2322}},
  keywords     = {{Biomarkers; Bronchiolitis Obliterans/etiology; Corticotropin-Releasing Hormone; Graft Rejection/diagnosis; Humans; Lung Transplantation/adverse effects; Matrix Metalloproteinase 9; Syndrome}},
  language     = {{eng}},
  pages        = {{1--11}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Corticotropin releasing hormone as an identifier of bronchiolitis obliterans syndrome}},
  url          = {{http://dx.doi.org/10.1038/s41598-022-12546-1}},
  doi          = {{10.1038/s41598-022-12546-1}},
  volume       = {{12}},
  year         = {{2022}},
}