Evidence map›Paper›PMID 26669438›Full record

ArticleGenome medicine2015

A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell transplantation.

Dirk S Paul, Allison Jones, Rob S Sellar, Neema P Mayor, Andrew Feber, Amy P Webster, Neuza Afonso, Ruhena Sergeant, Richard M Szydlo, Jane F Apperley and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Transplant genetics and genomics.Nature reviews. Genetics · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 1 country.

Dirk S PaulUCL Cancer Institute, University College London, London, UK. d.paul@ucl.ac.uk.
Allison JonesDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK.
Rob S SellarUCL Cancer Institute, University College London, London, UK.
Neema P MayorUCL Cancer Institute, University College London, London, UK.
Andrew FeberUCL Cancer Institute, University College London, London, UK.
Amy P WebsterUCL Cancer Institute, University College London, London, UK.
Neuza AfonsoDepartment of Haematology, University College London, Royal Free Hospital, London, UK.
Ruhena SergeantClinical Immunology, Imperial NHS Trust Hammersmith Hospital, London, UK.
Richard M SzydloCentre for Haematology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Jane F ApperleyCentre for Haematology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
Martin WidschwendterDepartment of Women's Cancer, UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK.
Stephen MackinnonUCL Cancer Institute, University College London, London, UK.
Steven G E MarshUCL Cancer Institute, University College London, London, UK.
J Alejandro MadrigalUCL Cancer Institute, University College London, London, UK.
Vardhman K RakyanBlizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. v.rakyan@qmul.ac.uk.
Karl S PeggsUCL Cancer Institute, University College London, London, UK. karl.peggs@ucl.ac.uk.
Stephan BeckUCL Cancer Institute, University College London, London, UK. s.beck@ucl.ac.uk.
University College Hospital · GBAnthony Nolan · GBCRUK Lung Cancer Centre of Excellence · GBImperial College Healthcare NHS Trust · GBThe Royal Free Hospital · GBCancer Research UK · GBQueen Mary University of London · GB

Funding

British Heart Foundation RG/08/014/24067Cancer Research UKDepartment of HealthMedical Research Council MR/L003120/1Wellcome Trust 99148
6 · The paper itself

Abstract

backgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. Here, we investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in human leukocyte antigen (HLA)-matched sibling recipients prior to T cell-depleted HSCT.

methodsWe measured DNA methylation levels genome-wide at single-nucleotide resolution in peripheral blood of 85 HSCT donors, matched to recipients with various transplant outcomes, with Illumina Infinium HumanMethylation450 BeadChips.

resultsUsing genome-wide DNA methylation profiling, we showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We discovered 31 DNA methylation marks in donors that associated with aGVHD severity status in recipients, and demonstrated strong predictive performance of these markers in internal cross-validation experiments (AUC = 0.98, 95% CI = 0.96-0.99). We replicated the top-ranked CpG classifier using an alternative, clinical DNA methylation assay (P = 0.039). In an independent cohort of 32 HSCT donors, we demonstrated the utility of the epigenetic classifier in the context of a T cell-replete conditioning regimen (P = 0.050).

conclusionsOur findings suggest that epigenetic typing of HSCT donors in a clinical setting may be used in conjunction with HLA genotyping to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome.

Indexed as

Tissue DonorsAdolescentAdultAgedDNA MethylationEpigenomicsFemaleGenotypeGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHLA AntigensHumansMaleMiddle AgedSiblingsT-LymphocytesHLA Antigens

Identifiers

PMID26669438
PMCPMC4681168
OpenAlexW2205159467

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.