Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients

Erwan Dumontet; Richard Danger; Parsia A. Vagefi; Maria Carlota Londoño; Annaïck Pallier; Juan José Lozano; Magali Giral; Nicolas Degauque; Jean Paul Soulillou; Marc Martínez-Llordella; Herman Lee; Marianne Latournerie; Karim Boudjema; Joelle Dulong; Karin Tarte; Alberto Sanchez-Fueyo; Sandy Feng; Sophie Brouard; Sophie Conchon

doi:10.1111/liv.12917

Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients

Erwan Dumontet, Richard Danger, Parsia A. Vagefi, Maria Carlota Londoño, Annaïck Pallier, Juan José Lozano, Magali Giral, Nicolas Degauque, Jean Paul Soulillou, Marc Martínez-Llordella, Herman Lee, Marianne Latournerie, Karim Boudjema, Joelle Dulong, Karin Tarte, Alberto Sanchez-Fueyo, Sandy Feng, Sophie Brouard, Sophie Conchon

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Background and Aims: The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established. Methods: In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL). Results: CLK show an intermediary phenotype with a higher percentage of peripheral CD19⁺CD24⁺CD38^Low memory B cells and Helios⁺ Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients. Conclusion: These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.

Original language	English (US)
Pages (from-to)	401-409
Number of pages	9
Journal	Liver International
Volume	36
Issue number	3
DOIs	https://doi.org/10.1111/liv.12917
State	Published - Mar 1 2016
Externally published	Yes

Keywords

Combined transplantation
Gene expression
Human
Kidney transplantation
Liver transplantation
MicroRNA
Phenotype

ASJC Scopus subject areas

Hepatology

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10.1111/liv.12917

Cite this

Dumontet, E., Danger, R., Vagefi, P. A., Londoño, M. C., Pallier, A., Lozano, J. J., Giral, M., Degauque, N., Soulillou, J. P., Martínez-Llordella, M., Lee, H., Latournerie, M., Boudjema, K., Dulong, J., Tarte, K., Sanchez-Fueyo, A., Feng, S., Brouard, S., & Conchon, S. (2016). Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients. Liver International, 36(3), 401-409. https://doi.org/10.1111/liv.12917

Dumontet, E, Danger, R, Vagefi, PA, Londoño, MC, Pallier, A, Lozano, JJ, Giral, M, Degauque, N, Soulillou, JP, Martínez-Llordella, M, Lee, H, Latournerie, M, Boudjema, K, Dulong, J, Tarte, K, Sanchez-Fueyo, A, Feng, S, Brouard, S & Conchon, S 2016, 'Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients', Liver International, vol. 36, no. 3, pp. 401-409. https://doi.org/10.1111/liv.12917

@article{f4e1c8f190114871be58da984671b1ee,

title = "Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients",

abstract = "Background and Aims: The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established. Methods: In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL). Results: CLK show an intermediary phenotype with a higher percentage of peripheral CD19+CD24+CD38Low memory B cells and Helios+ Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients. Conclusion: These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.",

keywords = "Combined transplantation, Gene expression, Human, Kidney transplantation, Liver transplantation, MicroRNA, Phenotype",

author = "Erwan Dumontet and Richard Danger and Vagefi, {Parsia A.} and Londo{\~n}o, {Maria Carlota} and Anna{\"i}ck Pallier and Lozano, {Juan Jos{\'e}} and Magali Giral and Nicolas Degauque and Soulillou, {Jean Paul} and Marc Mart{\'i}nez-Llordella and Herman Lee and Marianne Latournerie and Karim Boudjema and Joelle Dulong and Karin Tarte and Alberto Sanchez-Fueyo and Sandy Feng and Sophie Brouard and Sophie Conchon",

note = "Funding Information: We thank all the patients who participated in this study and the physicians who helped us recruit patients: JF. Subra, F. Villemain, C. Legendre, E. Thervet, FJ. Bemelman, G. Roussey, G. Orlando, A. Garnier, H. Jambon, H. Le Monies De Sagazan, L. Braun, C. No{\"e}l, E. Pillebout, MC. Moal, C. Cantarell, A. Hoitsma, M. Ranbant, A. Testa. Financial support: R.D. was supported by the “Fondation Centaure” (RTRS) which supports a French research network in transplantation and by a grant from the “Fondation pour la Recherche M{\'e}dicale” (FRM). E.D. was supported by a grant from the French National Academia of Medicine. INSERM U1064 was supported by the “Agence de la Biom{\'e}decine” and by the Association Fran{\c c}aise pour l''Etude du Foie, AFEF. PAV was supported by the ASTS/Novartis Fellowship in Transplantation Award. This work was carried out in the context of the IHU-Cesti project, which received financial support from the French government, managed by the National Research Agency (“Investment Into The Future” program ANR-10-IBHU-005), and from Nantes Metropole and the Pays de la Loire Region. The Institute of Liver Studies (KCL) is supported by the Medical Research Council (MRC) Centre for Transplantation, King''s College London, UK – MRC grant no. MR/J006742/1 and by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy''s and St Thomas'' NHS Foundation Trust and King''s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health . Conflict of interest: The authors do not have any disclosures to report. Funding Information: We thank all the patients who participated in this study and the physicians who helped us recruit patients: JF. Subra, F. Villemain, C. Legendre, E. Thervet, FJ. Bemelman, G. Roussey, G. Orlando, A. Garnier, H. Jambon, H. Le Monies De Sagazan, L. Braun, C. No?l, E. Pillebout, MC. Moal, C. Cantarell, A. Hoitsma, M. Ranbant, A. Testa. Financial support: R.D. was supported by the ?Fondation Centaure? (RTRS) which supports a French research network in transplantation and by a grant from the ?Fondation pour la Recherche M?dicale? (FRM). E.D. was supported by a grant from the French National Academia of Medicine. INSERM U1064 was supported by the ?Agence de la Biom?decine? and by the Association Fran?aise pour l''Etude du Foie, AFEF. PAV was supported by the ASTS/Novartis Fellowship in Transplantation Award. This work was carried out in the context of the IHU-Cesti project, which received financial support from the French government, managed by the National Research Agency (?Investment Into The Future? program ANR-10-IBHU-005), and from Nantes Metropole and the Pays de la Loire Region. The Institute of Liver Studies (KCL) is supported by the Medical Research Council (MRC) Centre for Transplantation, King''s College London, UK ? MRC grant no. MR/J006742/1 and by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy''s and St Thomas'' NHS Foundation Trust and King''s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health . Conflict of interest: The authors do not have any disclosures to report. Publisher Copyright: {\textcopyright} 2016 John Wiley & Sons A/S.",

year = "2016",

month = mar,

day = "1",

doi = "10.1111/liv.12917",

language = "English (US)",

volume = "36",

pages = "401--409",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients

AU - Dumontet, Erwan

AU - Danger, Richard

AU - Vagefi, Parsia A.

AU - Londoño, Maria Carlota

AU - Pallier, Annaïck

AU - Lozano, Juan José

AU - Giral, Magali

AU - Degauque, Nicolas

AU - Soulillou, Jean Paul

AU - Martínez-Llordella, Marc

AU - Lee, Herman

AU - Latournerie, Marianne

AU - Boudjema, Karim

AU - Dulong, Joelle

AU - Tarte, Karin

AU - Sanchez-Fueyo, Alberto

AU - Feng, Sandy

AU - Brouard, Sophie

AU - Conchon, Sophie

N1 - Funding Information: We thank all the patients who participated in this study and the physicians who helped us recruit patients: JF. Subra, F. Villemain, C. Legendre, E. Thervet, FJ. Bemelman, G. Roussey, G. Orlando, A. Garnier, H. Jambon, H. Le Monies De Sagazan, L. Braun, C. Noël, E. Pillebout, MC. Moal, C. Cantarell, A. Hoitsma, M. Ranbant, A. Testa. Financial support: R.D. was supported by the “Fondation Centaure” (RTRS) which supports a French research network in transplantation and by a grant from the “Fondation pour la Recherche Médicale” (FRM). E.D. was supported by a grant from the French National Academia of Medicine. INSERM U1064 was supported by the “Agence de la Biomédecine” and by the Association Française pour l''Etude du Foie, AFEF. PAV was supported by the ASTS/Novartis Fellowship in Transplantation Award. This work was carried out in the context of the IHU-Cesti project, which received financial support from the French government, managed by the National Research Agency (“Investment Into The Future” program ANR-10-IBHU-005), and from Nantes Metropole and the Pays de la Loire Region. The Institute of Liver Studies (KCL) is supported by the Medical Research Council (MRC) Centre for Transplantation, King''s College London, UK – MRC grant no. MR/J006742/1 and by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy''s and St Thomas'' NHS Foundation Trust and King''s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health . Conflict of interest: The authors do not have any disclosures to report. Funding Information: We thank all the patients who participated in this study and the physicians who helped us recruit patients: JF. Subra, F. Villemain, C. Legendre, E. Thervet, FJ. Bemelman, G. Roussey, G. Orlando, A. Garnier, H. Jambon, H. Le Monies De Sagazan, L. Braun, C. No?l, E. Pillebout, MC. Moal, C. Cantarell, A. Hoitsma, M. Ranbant, A. Testa. Financial support: R.D. was supported by the ?Fondation Centaure? (RTRS) which supports a French research network in transplantation and by a grant from the ?Fondation pour la Recherche M?dicale? (FRM). E.D. was supported by a grant from the French National Academia of Medicine. INSERM U1064 was supported by the ?Agence de la Biom?decine? and by the Association Fran?aise pour l''Etude du Foie, AFEF. PAV was supported by the ASTS/Novartis Fellowship in Transplantation Award. This work was carried out in the context of the IHU-Cesti project, which received financial support from the French government, managed by the National Research Agency (?Investment Into The Future? program ANR-10-IBHU-005), and from Nantes Metropole and the Pays de la Loire Region. The Institute of Liver Studies (KCL) is supported by the Medical Research Council (MRC) Centre for Transplantation, King''s College London, UK ? MRC grant no. MR/J006742/1 and by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy''s and St Thomas'' NHS Foundation Trust and King''s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health . Conflict of interest: The authors do not have any disclosures to report. Publisher Copyright: © 2016 John Wiley & Sons A/S.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background and Aims: The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established. Methods: In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL). Results: CLK show an intermediary phenotype with a higher percentage of peripheral CD19+CD24+CD38Low memory B cells and Helios+ Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients. Conclusion: These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.

AB - Background and Aims: The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established. Methods: In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL). Results: CLK show an intermediary phenotype with a higher percentage of peripheral CD19+CD24+CD38Low memory B cells and Helios+ Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients. Conclusion: These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.

KW - Combined transplantation

KW - Gene expression

KW - Human

KW - Kidney transplantation

KW - Liver transplantation

KW - MicroRNA

KW - Phenotype

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DO - 10.1111/liv.12917

M3 - Article

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SP - 401

EP - 409

JO - Liver International

JF - Liver International

IS - 3

ER -

Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients

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