Objectives and study
Post-transplantation lymphoproliferative disease (PTLD) is a serious complication in liver-transplanted children, most often related to Epstein-Barr virus (EBV) infection. The monitoring of EBV viral load using PCR is the easiest method to identify children at risk of PTLD. Yet a high viral load has a low specificity following pediatric liver transplantation. The role of NK cells in the control of EBV primary infection is increasingly recognized, and a modification of both their phenotype and function was demonstrated in thoracic transplanted children developing PTLD.
Between August 2013 and July 2015, we prospectively analyzed the rate of total NK cells and the proportion of their subpopulations using flow cytometry in 29 liver-transplanted children. In this population, we also measured the expression of three membrane receptors of NK cells: NKG2D, NKp46, and PD-1.
Five patients (17.2%) developed PTLD within 1 year post-transplantation (median: 84 days, range: 83-109 days). In these children, in the first trimester following the transplant, we detected an increased proportion of total NK cells (CD3-CD56±, 13.52% vs. 9.05%, p=0.0011), CD3-CD56dimCD16+ cells (63.08% vs. 43.18%, p=0.0011), and a reduced proportion of CD3-CD56bright cells (5.26% vs. 10.42%, p=0.0033). In this context, a test based on a CD3-CD56± cell rate ≥12.5% and CD3-CD56dimCD16+ cell rate ≥63% would offer a positive and negative predictive value of 100%, respectively, to detect children at risk of PTLD. These increased or decreased NK cell proportions were also observed in correlation with the EBV load (negative, low, high, or PTLD), yet without statistical significance (p=0.05-0.089). We found no differences in NK membrane receptor expressions between patients with or without PTLD.
The phenotypic analysis of NK cells using flow cytometry could be an easy and useful tool to monitor pediatric liver transplant recipients enabling us to quickly identify children at risk of PTLD. Pédiatrie NK cell phenotype as a risk marker of post-transplant lymphoproliferative disease in liver-transplanted children
1 Cliniques universitaires Saint-Luc, Service de Pédiatrie, avenue Hippocrate 10, B-1200 Bruxelles
² IREC (Institut de Recherche expérimentale), Université catholique de Louvain, Département de Biologie clinique, B-1200 Bruxelles