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Liver Int. 2016 Mar;36(3):401-9. doi: 10.1111/liv.12917. Epub 2015 Aug 8.

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

Author information

1
INSERM UMR 1064, Nantes, France.
2
CHU de Nantes, ITUN, Nantes, France.
3
Université de Nantes, Nantes, France.
4
Centre Hospitalier Universitaire Pontchaillou, Rennes, France.
5
Department of Liver Studies, Medical Research Council (MRC) Centre for Transplantation, School of Life Sciences & Medicine, King's College London University, London, UK.
6
Division of Transplantation Surgery, Massachusetts General Hospital, and Harvard medical school, Boston, MA, USA.
7
Liver Unit and Bioinformatic platform, Hospital Clinic Barcelona, Barcelona, Spain.
8
CIC Biothérapie, Nantes, France.
9
Department of Surgery, Division of Transplantation, University of California, San Francisco, CA, USA.
10
EFS Bretagne, Rennes, France.
11
INSERM UMR 917, Rennes, France.
12
CHU Nantes, CRB, Nantes, France.

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.

KEYWORDS:

combined transplantation; gene expression; human; kidney transplantation; liver transplantation; microRNA; phenotype

PMID:
26193627
PMCID:
PMC5395096
DOI:
10.1111/liv.12917
[Indexed for MEDLINE]
Free PMC Article

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