title: Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.
authors.affiliation: INSERM UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.|Centre Hospitalier Universitaire Pontchaillou, Rennes, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Dumontet
authors.affiliation: INSERM UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Department of Liver Studies, Medical Research Council (MRC) Centre for Transplantation, School of Life Sciences & Medicine, King's College London University, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Danger
authors.affiliation: Division of Transplantation Surgery, Massachusetts General Hospital, and Harvard medical school, Boston, MA, USA.
authors.forename: Parsia A
authors.initials: PA
authors.lastname: Vagefi
authors.affiliation: Liver Unit and Bioinformatic platform, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Maria-Carlota
authors.initials: MC
authors.lastname: Londoño
authors.affiliation: INSERM UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.
authors.forename: Annaïck
authors.initials: A
authors.lastname: Pallier
authors.affiliation: Liver Unit and Bioinformatic platform, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.affiliation: INSERM UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.|CIC Biothérapie, Nantes, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Giral
authors.affiliation: INSERM UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Degauque
authors.affiliation: INSERM UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.affiliation: Department of Liver Studies, Medical Research Council (MRC) Centre for Transplantation, School of Life Sciences & Medicine, King's College London University, London, UK.|Liver Unit and Bioinformatic platform, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Martínez-Llordella
authors.affiliation: Department of Surgery, Division of Transplantation, University of California, San Francisco, CA, USA.
authors.forename: Herman
authors.initials: H
authors.lastname: Lee
authors.affiliation: Centre Hospitalier Universitaire Pontchaillou, Rennes, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Latournerie
authors.affiliation: Centre Hospitalier Universitaire Pontchaillou, Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Boudjema
authors.affiliation: Centre Hospitalier Universitaire Pontchaillou, Rennes, France.|EFS Bretagne, Rennes, France.|INSERM UMR 917, Rennes, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Dulong
authors.affiliation: Centre Hospitalier Universitaire Pontchaillou, Rennes, France.|EFS Bretagne, Rennes, France.|INSERM UMR 917, Rennes, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.affiliation: Department of Liver Studies, Medical Research Council (MRC) Centre for Transplantation, School of Life Sciences & Medicine, King's College London University, London, UK.|Liver Unit and Bioinformatic platform, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sanchez-Fueyo
authors.affiliation: Department of Surgery, Division of Transplantation, University of California, San Francisco, CA, USA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Feng
authors.affiliation: INSERM UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|Université de Nantes, Nantes, France.|CIC Biothérapie, Nantes, France.|CHU Nantes, CRB, Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brouard
authors.affiliation: INSERM UMR 1064, Nantes, France.|Université de Nantes, Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Conchon
mesh_terms: D000368:Aged; D064591:Allografts; D005260:Female; D005602:France; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000097:blood*; D012495:San Francisco; D013030:Spain; D023001:Transplantation Tolerance / Q000187:drug effects / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D007166:Immunosuppressive Agents; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: combined transplantation; gene expression; human; kidney transplantation; liver transplantation; microRNA; phenotype