Cell-free DNA levels are increased in acute graft-versus-host disease.

Kroeze, Anna; Cornelissen, Anne S; Pascutti, M Fernanda; Verheij, Myrddin; Bulder, Ingrid; Klarenbeek, Sjoerd; Ait Soussan, Aicha; Hazenberg, Mette D; Nur, Erfan; van der Schoot, C Ellen; Voermans, Carlijn; Zeerleder, Sacha S (2022). Cell-free DNA levels are increased in acute graft-versus-host disease. European journal of haematology, 109(3), pp. 271-281. Wiley 10.1111/ejh.13806

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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

The aim of this study is to investigate the role of cfDNA as a marker of aGvHD.

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

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

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Zeerleder, Sacha Sergio

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1600-0609

Publisher:

Wiley

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

01 Sep 2022 09:20

Last Modified:

05 Dec 2022 16:23

Publisher DOI:

10.1111/ejh.13806

PubMed ID:

35617105

Uncontrolled Keywords:

acute graft versus host disease allogeneic hematopoietic stem cell transplantation biomarker cell-free nucleic acids nucleosomes

BORIS DOI:

10.48350/172552

URI:

https://boris.unibe.ch/id/eprint/172552

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