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 - 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
UR - http://www.scopus.com/inward/record.url?scp=84958944201&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958944201&partnerID=8YFLogxK
U2 - 10.1111/liv.12917
DO - 10.1111/liv.12917
M3 - Article
C2 - 26193627
AN - SCOPUS:84958944201
SN - 1478-3223
VL - 36
SP - 401
EP - 409
JO - Liver International
JF - Liver International
IS - 3
ER -