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

Christakoudi, Sofia (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 De Crespigny Pk, London SE5 8AF, England.;Imperial Coll London, Epidemiol & Biostat Dept, Norfolk Pl,St Marys Campus, London W2 1PG, England.
Runglall, Manohursingh (författare)
Guys & St Thomas NHS Fdn Trust & Kings Coll Londo, NIHR Biomed Res Ctr, London SE1 9RT, England.
Mobillo, Paula (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.
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Rebollo-Mesa, Irene (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 De Crespigny Pk, London SE5 8AF, England.;UCB Pharma SA, UCB Celltech, Brussels, Belgium.
Tsui, Tjir-Li (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.
Nova-Lamperti, Estefania (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Univ Concepcion, Pharm Fac, Dept Clin Biochem & Immunol, Lab Mol & Translat Immunol, Concepcion, Chile.
Taube, Catharine (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.
Norris, Sonia (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Modis, Ave Edison 19C, B-1300 Wavre, Belgium.
Kamra, Yogesh (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Kings Coll London, Peter Gorer Dept Immunobiol, London, England.
Hilton, Rachel (författare)
Augustine, Titus (författare)
Manchester Royal Infirm, Oxford Rd, Manchester M13 9WL, Lancs, England.;Kings Coll London, London, England.
Bhandari, Sunil (författare)
Hull Univ Teaching Hosp NHS Trust, Anlaby Rd, Kingston Upon Hull HU3 2JZ, N Humberside, England.;Kings Coll London, London, England.
Baker, Richard (författare)
St James Univ Hosp, Beckett St, Leeds LS9 7TF, W Yorkshire, England.;Kings Coll London, London, England.
Berglund, David, 1984- (författare)
Uppsala universitet,Klinisk immunologi,Kings Coll London, London, England.
Carr, Sue (författare)
Leicester Gen Hosp, Gwendolen Rd, Leicester LE5 4PW, Leics, England.;Kings Coll London, London, England.
Game, David (författare)
Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.;Kings Coll London, London, England.
Griffi, Sian (författare)
Cardiff & Vale Univ Hlth Board, Cardiff CF14 4XW, Wales.;Kings Coll London, London, England.
Kalra, Philip A. (författare)
Salford Royal NHS Fdn Trust, Stott Ln, Salford M6 8HD, Lancs, England.;Kings Coll London, London, England.
Lewis, Robert (författare)
Queen Alexandra Hosp, Southwick Hill Rd, Portsmouth PO6 3LY, Hants, England.;Kings Coll London, London, England.
Mark, Patrick B. (författare)
Univ Glasgow, Univ Ave, Glasgow G12 8QQ, Lanark, Scotland.;Kings Coll London, London, England.
Marks, Stephen D. (författare)
Great Ormond St Hosp Children NHS Fdn Trust, Dept Paediat Nephrol, Great Ormond St, London WC1N 3JH, England.;Univ Coll London Great Ormond St Inst Child Hlth, NIHR Great Ormond St Hosp Biomed Res Ctr, London WC1N, England.;Kings Coll London, London, England.
MacPhee, Iain (författare)
St George Hosp, Blackshaw Rd, London SW17 0QT, England.;Univ London, Inst Med & Biomed Educ, Cranmer Terrace, London SW17 0RE, England.;Kings Coll London, London, England.;AstraZeneca, Cambridge, England.
McKane, William (författare)
Northern Gen Hosp, Herries Rd, Sheffield S5 7AU, S Yorkshire, England.;Kings Coll London, London, England.
Mohaupt, Markus G. (författare)
Lindenhofgrp Berne, Internal Med, Bern, Switzerland.;Univ Bern, Bern, Switzerland.;Univ Nottingham, Sch Med, Nottingham NG5, England.;Kings Coll London, London, England.
Paz-Artal, Estela (författare)
Univ Hosp 12 Octubre, Dept Immunol & Imas12 Res Inst, Madrid, Spain.;Kings Coll London, London, England.
Kon, Sui Phin (författare)
Kings Coll Hosp NHS Fdn Trust, Denmark Hill, London SE5 9RS, England.;Kings Coll London, London, England.
Seron, Daniel (författare)
Hosp Univ Vall dHebron, Passeig Vall dHebron 119-129, Barcelona 08035, Spain.;Kings Coll London, London, England.
Sinha, Manish D. (författare)
Evelina London Childrens Hosp, Bridge Rd, London SE1 7EH, England.;Guys Hosp, Kings Hlth Partners, London SE1 9RT, England.;Kings Coll London, London, England.
Tucker, Beatriz (författare)
Kings Coll Hosp NHS Fdn Trust, Denmark Hill, London SE5 9RS, England.;Kings Coll London, London, England.
Viklick, Ondrej (författare)
IKEM, Videnska 1958-9, Prague 14021 4, Czech Republic.;Kings Coll London, London, England.
Stahl, Daniel (författare)
Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 De Crespigny Pk, London SE5 8AF, England.
Lechler, Robert I. (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Guys Hosp, Kings Hlth Partners, London SE1 9RT, England.
Lord, Graham M. (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Guys & St Thomas NHS Fdn Trust & Kings Coll Londo, NIHR Biomed Res Ctr, London SE1 9RT, England.;Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.;Univ Manchester, Fac Biol Med & Hlth, Manchester, Lancs, England.
Hernandez-Fuentes, Maria P. (författare)
Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.;Guys Hosp, Kings Hlth Partners, London SE1 9RT, England.
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Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 De Crespigny Pk, London SE5 8AF, England.;Imperial Coll London, Epidemiol & Biostat Dept, Norfolk Pl,St Marys Campus, London W2 1PG, England. Guys & St Thomas NHS Fdn Trust & Kings Coll Londo, NIHR Biomed Res Ctr, London SE1 9RT, England. (creator_code:org_t)
Elsevier BV, 2020
2020
Engelska.
Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 58
Relaterad länk:
https://doi.org/10.1...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background: Kidney 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. Methods: We 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. Findings: IS 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. Interpretation: We 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. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license. (http://creativecommons.org/licenses/by/4.0/)

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Nyckelord

Kidney
Transplantation
Operational Tolerance
Biomarkers
Immunosuppressive Drugs
RT-qPCR

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