-
Je něco špatně v tomto záznamu ?
Development and validation of the first consensus gene-expression signature of operational tolerance in kidney transplantation, incorporating adjustment for immunosuppressive drug therapy
S. Christakoudi, M. Runglall, P. Mobillo, I. Rebollo-Mesa, TL. Tsui, E. Nova-Lamperti, C. Taube, S. Norris, Y. Kamra, R. Hilton, T. Augustine, S. Bhandari, R. Baker, D. Berglund, S. Carr, D. Game, S. Griffin, PA. Kalra, R. Lewis, PB. Mark, SD....
Jazyk angličtina Země Nizozemsko
Typ dokumentu srovnávací studie, časopisecké články
NLK
Directory of Open Access Journals
od 2014
PubMed Central
od 2014
Europe PubMed Central
od 2014 do 2020
Open Access Digital Library
od 2014-01-01
Open Access Digital Library
od 2014-11-01
Open Access Digital Library
od 2014-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2014
- MeSH
- dospělí MeSH
- genové regulační sítě * účinky léků MeSH
- imunosupresiva farmakologie terapeutické užití MeSH
- konsensus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- logistické modely MeSH
- rejekce štěpu genetika prevence a kontrola MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- studie případů a kontrol MeSH
- transplantace ledvin škodlivé účinky MeSH
- transplantační tolerance * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
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. FUNDING: FP7-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].
Cardiff and Vale University Health Board Cardiff CF14 4XW UK
Evelina 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
Hospital Universitario Vall d'Hebrón Passeig de la Vall d'Hebron 119 129 08035 Barcelona Spain
Hull University Teaching Hospitals NHS Trust Anlaby Rd Hull HU3 2JZ UK
Internal Medicine Lindenhofgruppe Berne Switzerland
King's College Hospital NHS Foundation Trust Denmark Hill London SE5 9RS UK
King's Health Partners Guy's Hospital London SE1 9RT UK
Leicester General Hospital Gwendolen Rd Leicester LE5 4PW UK
Manchester Royal Infirmary Oxford Rd Manchester M13 9WL UK
MRC Centre for Transplantation King's College London Great Maze Pond London SE1 9RT UK
Northern General Hospital Herries Rd Sheffield S5 7AU UK
Queen Alexandra Hospital Southwick Hill Rd Cosham Portsmouth PO6 3LY UK
Salford Royal NHS Foundation Trust Stott Ln Salford M6 8HD UK
School of Medicine University of Nottingham Nottingham NG5 1PB UK
St James's University Hospital Beckett St Leeds LS9 7TF UK
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc21020288
- 003
- CZ-PrNML
- 005
- 20210830101917.0
- 007
- ta
- 008
- 210728s2020 ne f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.ebiom.2020.102899 $2 doi
- 035 __
- $a (PubMed)32707447
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a ne
- 100 1_
- $a Christakoudi, Sofia $u MRC 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
- 245 10
- $a Development and validation of the first consensus gene-expression signature of operational tolerance in kidney transplantation, incorporating adjustment for immunosuppressive drug therapy / $c S. Christakoudi, M. Runglall, P. Mobillo, I. Rebollo-Mesa, TL. Tsui, E. Nova-Lamperti, C. Taube, S. Norris, Y. Kamra, R. Hilton, T. Augustine, S. Bhandari, R. Baker, D. Berglund, S. Carr, D. Game, S. Griffin, PA. Kalra, R. Lewis, PB. Mark, SD. Marks, I. MacPhee, W. McKane, MG. Mohaupt, E. Paz-Artal, SP. Kon, D. Serón, MD. Sinha, B. Tucker, O. Viklický, D. Stahl, RI. Lechler, GM. Lord, MP. Hernandez-Fuentes
- 520 9_
- $a 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. FUNDING: FP7-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].
- 650 _2
- $a dospělí $7 D000328
- 650 _2
- $a senioři $7 D000368
- 650 _2
- $a studie případů a kontrol $7 D016022
- 650 _2
- $a konsensus $7 D032921
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a stanovení celkové genové exprese $x metody $7 D020869
- 650 12
- $a genové regulační sítě $x účinky léků $7 D053263
- 650 _2
- $a rejekce štěpu $x genetika $x prevence a kontrola $7 D006084
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a imunosupresiva $x farmakologie $x terapeutické užití $7 D007166
- 650 _2
- $a transplantace ledvin $x škodlivé účinky $7 D016030
- 650 _2
- $a logistické modely $7 D016015
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a lidé středního věku $7 D008875
- 650 _2
- $a kvantitativní polymerázová řetězová reakce $7 D060888
- 650 12
- $a transplantační tolerance $7 D023001
- 655 _2
- $a srovnávací studie $7 D003160
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Runglall, Manohursingh $u NIHR Biomedical Research Centre at Guy's & St Thomas' NHS Foundation Trust and King's College London, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Mobillo, Paula $u MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Rebollo-Mesa, Irene $u MRC 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
- 700 1_
- $a Tsui, Tjir-Li $u MRC 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
- 700 1_
- $a Nova-Lamperti, Estefania $u MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Taube, Catharine $u MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Norris, Sonia $u MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Kamra, Yogesh $u MRC Centre for Transplantation, King's College London, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Hilton, Rachel $u Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Augustine, Titus $u Manchester Royal Infirmary, Oxford Rd, Manchester M13 9WL, UK
- 700 1_
- $a Bhandari, Sunil $u Hull University Teaching Hospitals NHS Trust, Anlaby Rd, Hull HU3 2JZ, UK
- 700 1_
- $a Baker, Richard $u St James's University Hospital, Beckett St, Leeds LS9 7TF, UK
- 700 1_
- $a Berglund, David $u Department of Immunology, Genetics and Pathology, Uppsala University, Rudbecklaboratoriet, 751 85 Uppsala, Sweden
- 700 1_
- $a Carr, Sue $u Leicester General Hospital, Gwendolen Rd, Leicester LE5 4PW, UK
- 700 1_
- $a Game, David $u Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK
- 700 1_
- $a Griffin, Sian $u Cardiff and Vale University Health Board, Cardiff CF14 4XW, UK
- 700 1_
- $a Kalra, Philip A $u Salford Royal NHS Foundation Trust, Stott Ln, Salford M6 8HD, UK
- 700 1_
- $a Lewis, Robert $u Queen Alexandra Hospital, Southwick Hill Rd, Cosham, Portsmouth PO6 3LY, UK
- 700 1_
- $a Mark, Patrick B $u University of Glasgow, University Avenue, Glasgow G12 8QQ, UK
- 700 1_
- $a Marks, Stephen D $u Department 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
- 700 1_
- $a MacPhee, Iain $u St 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
- 700 1_
- $a McKane, William $u Northern General Hospital, Herries Rd, Sheffield S5 7AU, UK
- 700 1_
- $a Mohaupt, Markus G $u Internal Medicine, Lindenhofgruppe Berne, Switzerland; University of Bern, Berne, Switzerland; School of Medicine, University of Nottingham, Nottingham NG5 1PB, UK
- 700 1_
- $a Paz-Artal, Estela $u Department of Immunology and imas12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain
- 700 1_
- $a Kon, Sui Phin $u King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK
- 700 1_
- $a Serón, Daniel $u Hospital Universitario Vall d'Hebrón, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain
- 700 1_
- $a Sinha, Manish D $u Evelina 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
- 700 1_
- $a Tucker, Beatriz $u King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK
- 700 1_
- $a Viklický, Ondrej $u Transplantační laboratoř, Institut klinické a experimentální medicíny (IKEM), Vídeňská 1958/9, 140 21 Praha 4, Czech Republic
- 700 1_
- $a Stahl, Daniel $u Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK
- 700 1_
- $a Lechler, Robert I $u MRC 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
- 700 1_
- $a Lord, Graham M $u MRC 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
- 700 1_
- $a Hernandez-Fuentes, Maria P $u MRC 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
- 773 0_
- $w MED00190061 $t EBioMedicine $x 2352-3964 $g Roč. 58, č. - (2020), s. 102899
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/32707447 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20210728 $b ABA008
- 991 __
- $a 20210830101917 $b ABA008
- 999 __
- $a ok $b bmc $g 1690966 $s 1140734
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2020 $b 58 $c - $d 102899 $e 20200721 $i 2352-3964 $m EBioMedicine $n EBioMedicine $x MED00190061
- LZP __
- $a Pubmed-20210728
