Chronic graft-versus-host disease is characterized by high levels and distinctive tissue-of-origin patterns of cell-free DNA

Pang, Yifan; Andargie, Temesgen E.; Jang, Moon Kyoo; Kong, Hyesik; Park, Woojin; Hill, Thomas; Redekar, Neelam; Fu, Yi-Ping; Parth, Desai A.; Holtzman, Noa G.; Pavletic, Steven Z.; Agbor-Enoh, Sean

doi:10.1016/j.isci.2023.108160

Cited by 2 publications

(1 citation statement)

References 37 publications

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“…Instead, epigenetic modifications can be used to identify cfDNA that is recipient or allograft-derived by using tissue-and cell-type specific marks that are independent of genotype differences between the donor and recipient (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Allograft injury can thus be detected in an organ specific fashion, which is of critical importance in recipients of multi-organ transplants and recipients of hematopoietic cell transplant (HCT) who develop Graft-versus-Host disease (GvHD) (30)(31)(32). Also, the allograft as well as recipient organs are impacted by the transplant process as well as by subsequent treatments that can lead to tissue damage and remodeling.…”

Section: Introductionmentioning

confidence: 99%

Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant

McNamara,

Jain,

Oza

et al. 2024

Preprint

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Post-transplant complications reduce allograft and recipient survival. Current approaches for detecting allograft injury non-invasively are limited and do not differentiate between cellular mechanisms. Here, we monitor cellular damages after liver transplants from cell-free DNA (cfDNA) fragments released from dying cells into the circulation. We analyzed 130 blood samples collected from 44 patients at different time points after transplant. Sequence-based methylation of cfDNA fragments were mapped to patterns established to identify cell types in different organs. For liver cell types DNA methylation patterns and multi-omic data integration show distinct enrichment in open chromatin and regulatory regions functionally important for the respective cell types. We find that multi-tissue cellular damages post-transplant recover in patients without allograft injury during the first post-operative week. However, sustained elevation of hepatocyte and biliary epithelial cfDNA beyond the first week indicates early-onset allograft injury. Further, cfDNA composition differentiates amongst causes of allograft injury indicating the potential for non-invasive monitoring and timely intervention.

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Section: Introductionmentioning

confidence: 99%

Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant

McNamara,

Jain,

Oza

et al. 2024

Preprint

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Cell-free RNA Liquid Biopsy to Monitor Hematopoietic Stem Cell Transplantation

Loy,

Cheng,

Gonzalez-Bocco

et al. 2024

Preprint

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Hematopoietic Stem Cell Transplantation (HSCT) is one of the oldest and most successful immunotherapies. Yet, despite long-standing success in the use of HSCT for the treatment of blood cancers and severe immune disorders, monitoring post-transplant complications remains a challenge due to a lack of informative diagnostic tests. Here, we investigate the utility of cell-free RNA (cfRNA) in plasma as a liquid biopsy to monitor allogeneic HSCT recipients during and after treatment. We assayed longitudinal samples from 92 HSCT recipients by cfRNA sequencing and show that cfRNA provides insight into treatment and recovery trajectories, immune dynamics in response to transplantation, infection, and solid-tissue injury associated with Graft-Versus-Host Disease. Collectively, our results provide support for the use of plasma cfRNA profiling to monitor complications of HSCT.

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Chronic graft-versus-host disease is characterized by high levels and distinctive tissue-of-origin patterns of cell-free DNA

Cited by 2 publications

References 37 publications

Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant

Circulating, cell-free methylated DNA indicates cellular sources of allograft injury after liver transplant

Cell-free RNA Liquid Biopsy to Monitor Hematopoietic Stem Cell Transplantation

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