Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.


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Authors
Ferdinand, John Robert  ORCID logo  https://orcid.org/0000-0003-0936-0128
Morrison, Morvern Isabel 
Andreasson, Anders 
Charlton, Catriona 
Chhatwal, Alisha Kaur 
Abstract

BACKGROUND: Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined. METHODS: We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non-transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion. RESULTS: We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non-transplantable lungs, while CHIT-1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non-transplantable lungs (AUC .81). CONCLUSIONS: Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.

Description

Funder: NIHR Blood and Transplant Unit


Funder: NIHR Newcastle Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012295


Funder: NIHR Cambridge Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100018956

Keywords
artificial organs, chemokine receptors, chemokines, clinical trial, support devices: lung, Biomarkers, Humans, Lung, Lung Transplantation, Perfusion, Tissue Donors
Journal Title
Clin Transplant
Conference Name
Journal ISSN
0902-0063
1399-0012
Volume Title
Publisher
Wiley
Sponsorship
Medical Research Council (MR/N024907/1)