Evidence map›Paper›PMID 32707447›Full record

ArticleEBioMedicine2020

Development and validation of the first consensus gene-expression signature of operational tolerance in kidney transplantation, incorporating adjustment for immunosuppressive drug therapy.

Sofia Christakoudi, Manohursingh Runglall, Paula Mobillo, Irene Rebollo-Mesa, Tjir-Li Tsui, Estefania Nova-Lamperti, Catharine Taube, Sonia Norris, Yogesh Kamra, Rachel Hilton and 24 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Single-cell RNA sequencing reveals peripheral blood mononuclear immune cell landscape associated with operational tolerance in a kidney transplant recipient.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023
    Article
  5. Article
  6. Review
  7. Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis.International journal of molecular sciences · 2021
    Review
  8. Review
  9. Article
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

34 authors.

Sofia ChristakoudiMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK. Electronic address: s.christakoudi@imperial.ac.uk.
Manohursingh RunglallNIHR Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust and King's College London, Great Maze Pond, London SE1 9RT, UK.
Paula MobilloMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK.
Irene Rebollo-MesaMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK.
Tjir-Li TsuiMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Estefania Nova-LampertiMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK.
Catharine TaubeMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK.
Sonia NorrisMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK.
Yogesh KamraMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK.
Rachel HiltonGuy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Titus AugustineManchester Royal Infirmary, Oxford Rd, Manchester M13 9WL, UK.
Sunil BhandariHull University Teaching Hospitals NHS Trust, Anlaby Rd, Hull HU3 2JZ, UK.
Richard BakerSt James's University Hospital, Beckett St, Leeds LS9 7TF, UK.
David BerglundDepartment of Immunology, Genetics and Pathology, Uppsala University, Rudbecklaboratoriet, 751 85 Uppsala, Sweden.
Sue CarrLeicester General Hospital, Gwendolen Rd, Leicester LE5 4PW, UK.
David GameGuy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Sian GriffinCardiff and Vale University Health Board, Cardiff CF14 4XW, UK.
Philip A KalraSalford Royal NHS Foundation Trust, Stott Ln, Salford M6 8HD, UK.
Robert LewisQueen Alexandra Hospital, Southwick Hill Rd, Cosham, Portsmouth PO6 3LY, UK.
Patrick B MarkUniversity of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Stephen D MarksDepartment of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK; University College London Great Ormond Street Institute of Child Health, NIHR Great Ormond Street Hospital Biomedical Research Centre, London WC1N 1EH, UK.
Iain MacPheeSt George's Hospital, Blackshaw Rd, London SW17 0QT, UK & Institute of Medical and Biomedical Education, St George's, University of London, Cranmer Terrace, London SW17 0RE.
William McKaneNorthern General Hospital, Herries Rd, Sheffield S5 7AU, UK.
Markus G MohauptInternal Medicine, Lindenhofgruppe Berne, Switzerland; University of Bern, Berne, Switzerland; School of Medicine, University of Nottingham, Nottingham NG5 1PB, UK.
Estela Paz-ArtalDepartment of Immunology and imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain.
Sui Phin KonKing's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK.
Daniel SerónHospital Universitario Vall d'Hebrón, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
Manish D SinhaEvelina London Children's Hospital, Westminster Bridge Rd, Lambeth, London SE1 7EH, UK; Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK; King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
Beatriz TuckerKing's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK.
Ondrej ViklickýTransplantační laboratoř, Institut klinické a experimentální medicíny (IKEM), Vídeňská 1958/9, 140 21 Praha 4, Czech Republic.
Daniel StahlBiostatistics and Health Informatics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK.
Robert I LechlerMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
Graham M LordMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; NIHR Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust and King's College London, Great Maze Pond, London SE1 9RT, UK; Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
Maria P Hernandez-FuentesMRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK; King's Health Partners, Guy's Hospital, London SE1 9RT, UK.

Funding

Medical Research Council MR/J006742/1
6 · The paper itself

Abstract

backgroundKidney transplant recipients (KTRs) with "operational tolerance" (OT) maintain a functioning graft without immunosuppressive (IS) drugs, thus avoiding treatment complications. Nevertheless, IS drugs can influence gene-expression signatures aiming to identify OT among treated KTRs.

methodsWe compared five published signatures of OT in peripheral blood samples from 18 tolerant, 183 stable, and 34 chronic rejector KTRs, using gene-expression levels with and without adjustment for IS drugs and regularised logistic regression.

findingsIS drugs explained up to 50% of the variability in gene-expression and 20-30% of the variability in the probability of OT predicted by signatures without drug adjustment. We present a parsimonious consensus gene-set to identify OT, derived from joint analysis of IS-drug-adjusted expression of five published signature gene-sets. This signature, including CD40, CTLA4, HSD11B1, IGKV4-1, MZB1, NR3C2, and RAB40C genes, showed an area under the curve 0⋅92 (95% confidence interval 0⋅88-0⋅94) in cross-validation and 0⋅97 (0⋅93-1⋅00) in six months follow-up samples.

interpretationWe advocate including adjustment for IS drug therapy in the development stage of gene-expression signatures of OT to reduce the risk of capturing features of treatment, which could be lost following IS drug minimisation or withdrawal. Our signature, however, would require further validation in an independent dataset and a biomarker-led trial.

fundingFP7-HEALTH-2012-INNOVATION-1 [305147:BIO-DrIM] (SC,IR-M,PM,DSt); MRC [G0801537/ID:88245] (MPH-F); MRC [MR/J006742/1] (IR-M); Guy's&StThomas' Charity [R080530]&[R090782]; CONICYT-Bicentennial-Becas-Chile (EN-L); EU:FP7/2007-2013 [HEALTH-F5-2010-260687: The ONE Study] (MPH-F); Czech Ministry of Health [NV19-06-00031] (OV); NIHR-BRC Guy's&StThomas' NHS Foundation Trust and KCL (SC); UK Clinical Research Networks [portfolio:7521].

Indexed as

Gene Regulatory NetworksTransplantation ToleranceAdultAgedCase-Control StudiesConsensusFemaleGene Expression ProfilingGraft RejectionHumansImmunosuppressive AgentsKidney TransplantationLogistic ModelsMaleMiddle AgedReal-Time Polymerase Chain ReactionImmunosuppressive AgentsBiomarkersImmunosuppressive DrugsKidneyOperational ToleranceRT-qPCRTransplantation

Identifiers

PMID32707447
PMCPMC7374249

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Registered trials

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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.