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

^*Corresponding author for this work

King's College London

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

11 Citations (Scopus)

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
Pages (from-to)	401–409
Number of pages	9
Journal	LIVER INTERNATIONAL
Volume	36
Issue number	3
Early online date	8 Aug 2015
DOIs	https://doi.org/10.1111/liv.12917
Publication status	Published - Mar 2016

Keywords

Combined transplantation
Gene expression
Human
Kidney transplantation
Liver transplantation
MicroRNA
Phenotype

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10.1111/liv.12917

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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

@article{e20f96617a0445fda471e7b4713ff4dd,

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

abstract = "Background and AimsThe 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.MethodsIn 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).ResultsCLK 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.ConclusionThese 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",

year = "2016",

month = mar,

doi = "10.1111/liv.12917",

language = "English",

volume = "36",

pages = "401–409",

journal = "LIVER INTERNATIONAL",

issn = "1478-3223",

publisher = "Wiley-Blackwell",

number = "3",

}

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

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

PY - 2016/3

Y1 - 2016/3

N2 - Background and AimsThe 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.MethodsIn 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).ResultsCLK 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.ConclusionThese data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.

AB - Background and AimsThe 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.MethodsIn 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).ResultsCLK 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.ConclusionThese 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

UR - http://www.scopus.com/inward/record.url?scp=84938802063&partnerID=8YFLogxK

U2 - 10.1111/liv.12917

DO - 10.1111/liv.12917

M3 - Article

SN - 1478-3223

VL - 36

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

Abstract

Keywords

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