Cell-free DNA levels are increased in acute graft-versus-host disease.
acute graft versus host disease
allogeneic hematopoietic stem cell transplantation
biomarker
cell-free nucleic acids
nucleosomes
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
revised:
20
05
2022
received:
09
01
2022
accepted:
23
05
2022
pubmed:
27
5
2022
medline:
12
8
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
Cell-free DNA (cfDNA) and nucleosomes, consisting of cfDNA and histones, are markers of cell activation and damage. In systemic inflammation these markers predict severity and fatality. However, the role of cfDNA in acute Graft-versus-Host Disease (aGvHD), a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), is unknown. The aim of this study is to investigate the role of cfDNA as a marker of aGvHD. We followed nucleosome levels in 37 allogeneic HSCT patients and an established xenotransplantation mouse model. We determined the origin of cfDNA with a species-specific polymerase chain reaction. In the plasma of aGvHD patients, nucleosome levels significantly increased around the time of aGvHD diagnosis compared to pretransplant, concurrently with a significant increase of known aGvHD markers ST2 and REG3α. In mice, we confirmed that nucleosomes were elevated during clinically detectable aGvHD. We found cfDNA to be mainly of human origin and to a lesser extent of mouse origin, indicating that cfDNA is released by (proliferating) human xeno-reactive PBMC and damaged mouse cells. We show increased cfDNA both in an aGvHD mouse model and in aGvHD patients. We also demonstrate that donor hematopoietic cells and to a lesser degree (damaged) host cells are the cellular source of cfDNA in aGvHD. We propose that nucleosomes and cfDNA might be an additive marker for aGvHD.
Sections du résumé
BACKGROUND
BACKGROUND
Cell-free DNA (cfDNA) and nucleosomes, consisting of cfDNA and histones, are markers of cell activation and damage. In systemic inflammation these markers predict severity and fatality. However, the role of cfDNA in acute Graft-versus-Host Disease (aGvHD), a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), is unknown.
OBJECTIVE
OBJECTIVE
The aim of this study is to investigate the role of cfDNA as a marker of aGvHD.
METHODS
METHODS
We followed nucleosome levels in 37 allogeneic HSCT patients and an established xenotransplantation mouse model. We determined the origin of cfDNA with a species-specific polymerase chain reaction.
RESULTS
RESULTS
In the plasma of aGvHD patients, nucleosome levels significantly increased around the time of aGvHD diagnosis compared to pretransplant, concurrently with a significant increase of known aGvHD markers ST2 and REG3α. In mice, we confirmed that nucleosomes were elevated during clinically detectable aGvHD. We found cfDNA to be mainly of human origin and to a lesser extent of mouse origin, indicating that cfDNA is released by (proliferating) human xeno-reactive PBMC and damaged mouse cells.
CONCLUSION
CONCLUSIONS
We show increased cfDNA both in an aGvHD mouse model and in aGvHD patients. We also demonstrate that donor hematopoietic cells and to a lesser degree (damaged) host cells are the cellular source of cfDNA in aGvHD. We propose that nucleosomes and cfDNA might be an additive marker for aGvHD.
Substances chimiques
Biomarkers
0
Cell-Free Nucleic Acids
0
Nucleosomes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
271-281Subventions
Organisme : Landsteiner Foundation for Blood Transfusion Research
ID : 1101
Organisme : Landsteiner Foundation for Blood Transfusion Research
ID : 1719
Organisme : Sanquin Research
ID : PPOC 13-027
Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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