Donor Chimerism, Kir Ligand Mismatch and Cytokine Levels (TnfÃŽÂ±, Il17, Gmcsf, l1ÃŽÂ²) and their Association with Graft Rejection in Liver Transplant Recipients
|Rosa Ayala1,6*, Inmaculada Rapado1*, Antonio Perez2, Silvia Grande1, Alicia Arenas1, Alvaro García Sesma5, Jose Luis Vicario3, Manuel Serrano4, Jose Angel Martinez4, Santiago Barrio1, Carmelo Loinaz5, Carlos Jimenez5,6, Enrique Moreno5,6 and Joaquin Martinez-Lopez1,6|
|1Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain|
|2Department of Pediatrics, Hospital U. La Paz, Madrid, Spain|
|3Department of Histocompatibility, Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain|
|4Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain|
|5Department of General Surgery, Alimentary Tract and Abdominal Organ Transplantation, Hospital Universitario 12 de Octubre, Madrid, Spain|
|6Universidad Complutense de Madrid, Madrid, Spain|
|*Corresponding Authors :||Rosa Ayala
Laboratorio de Biología Molecular
Servicio de Hematología. Hospital Universitario 12 de Octubre
Av Córdoba, SN, 28041 Madrid, Spain
E-mail: [email protected]
Department of Hematology
Hospital Universitario 12 de Octubre
E-mail: [email protected]
|Received: January 25, 2016; Accepted: April 05, 2016; Published: April 08, 2016|
|Citation: Ayala R, Rapado I, Perez A, Grande S, Arenas A, et al. (2016) Donor Chimerism, Kir Ligand Mismatch and Cytokine Levels (Tnfα, Il17, Gmcsf, Il1β) and their Association with Graft Rejection in Liver Transplant Recipients. J Clin Cell Immunol 7:407. doi:10.4172/2155-9899.1000407|
|Copyright: © 2016 Ayala R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
Background: The aim of the study is to design a predictive model of graft rejection in liver transplant recipients based on donor chimerism (DC) quantification, functional study of Natural Killer cells and cytokine levels.
Methods: Seventy-four liver transplant recipients and their respective donors were studied, providing a total of 468 post-transplantation samples in the chimerism study. A total of 23 Liver Transplant patients and their respective donors took part in HLA typing and KIR genotyping, phenotyping, and cytotoxicity studies. 62 liver transplant recipients were analyzed in this cytokine study (62 pre-transplant and 109 post-transplant serum samples). Chimerism study was carried out by quantitative real time PCRs and 7 indels and 14 SNPs were detected with TM probes. A study of NK-cell subsets was performed on fresh samples by multiparametric flow cytometry (Becton Dickinson). KIR genotyping and KIR ligand were analyzed by PCR with a KIR typing Kit (Milteny Biotec). Cytotoxicity assays were monitored in a conventional 2-hour europium-TDA release assay (Perkin-Elmer). Biorad “17-plex Kit on a luminex” platform was used for cytokines measurement.
Results and conclusions: High chimerism levels during the first months after transplantation were related to a lower probability of rejection. A CD56 bright NK cell subset appeared to dominate the early post-transplant period following liver transplantation. A tendency to high frequency of graft rejection was observed in cases with KIR-ligand mismatches. Donors lacking C1 ligands exhibited increased risk of acute rejection. Cytokine levels predicted events in liver transplant recipients: low TNFα levels in pre-transplant recipient samples were associated with liver disease relapse and low IL17 and TNFα levels and high GMCSF and IL1β levels were associated with low rejection free survival. Finally IL6 levels showed an adverse impact on recipient overall survival.