Markers of operational immune tolerance after pediatric liver transplantation in patients under immunosuppression

Abstract

A prospective identification of the estimated 20-50% of pediatric LTX recipients developing operational tolerance would be of great clinical advantage. So far markers of immune tolerance - T-cell subpopulations or gene expression profiles - have been investigated only retrospectively in successfully weaned patients. Fifty children aged 8-265 months (median 89) were investigated 1-180 months (median 44) after LTX under ongoing immunosuppression. T-cell subpopulations were measured during regular post-transplant visits using FACS (Vδ1- vs. Vδ2-γδ-T cells and Tregs). A Vδ1/Vδ2-γδ-T-cell ratio ≥1.42 previously reported in operational tolerance was found in 12 of 50 (24%) patients. In analogy, a Treg count ≥44 per μL was found in 35 of 50 (70%) patients and a Treg proportion ≥2.23% of CD3(+) -T cells in 39 of 50 (78%) patients. Only 9 of 50 patients (18%) fulfilled both criteria. The parameters Vδ1/Vδ2-γδ-T-cell ratio and Tregs were not significantly correlated to each other or with donor type or immunosuppression. Vδ1/Vδ2-γδ-T-cell ratio was more stable in serial examinations compared with Treg analyses. The observed proportion of 18% pediatric LTX patients with potential operational tolerance is in accordance with previous reports. However, clinical experience shows that rejections may happen even after long-time weaning of immunosuppression. This suggests that operational tolerance is a dynamic process, with uncertain prediction by Vδ1/Vδ2-γδ-T-cell ratio and/or Tregs under immunosuppression.

Utility of neonatal donors in pediatric liver transplantation: A single‐center experience

“…Of note, only one recipient in this study had a GRWR less than 1%, and this recipient did not develop SFSS, but hepatic artery thrombosis occurred. These data were in consistent with the previous reports that small liver graft was associated with hepatic artery complications . None of the recipients in group 3 developed SFSS, and the incidence rate was significant lower than groups 1 and 2.…”

“…In spite of the fact that neonatal (group 1) and infant (group 2) grafts seemed to have higher rate of SFSS, the recipients in these two groups showed favorable outcome in acute rejection, and the recipients in group 3 exhibited significantly higher rate of acute rejection compared with the combination of groups 1 and 2 in our study. It has long been claimed that immune tolerance is more likely to be induced in children due to the immatureness of immune system . The immunosuppressive protocol in our center for recipient younger than 6 years old is the combination of tacrolimus and steroids, unlike adult recipients, MMF is not considered unless in recipients who received ABO incompatible donors or had high risk of postoperative immune rejection.…”

Tolerancia operacional en un receptor pediátrico de trasplante hepático. Caso clínico

“…3,[8][9][10][11] Cargas VEB (log) Dosaje FK (ng/ml) Desde los primeros reportes de buena evolución a pesar de la mala adherencia al tratamiento, 1,2 varios centros describen sus resultados respecto de la tolerancia operacional, pero la aplicabilidad de estas experiencias está limitada por la actual imposibilidad de predecir quiénes son candidatos a tolerar y quiénes requieren inmunosupresión sostenida. 5 Si bien algunos autores discuten si suspender la medicación implica una mejoría de la calidad de vida de los pacientes trasplantados, ya que no garantiza el fin del monitoreo, sino que demanda aún más y frecuentes controles de seguimiento, 12 la mayoría coincide en las ventajas que plantearía minimizar y suspender la inmunosupresión en cuanto a las complicaciones relativas a esta medicación. En un reciente modelo hipotético de cohorte de pacientes pediátricos, Mohammad y cols., plantean, además de la mejoría en la supervivencia de los pacientes sin medicación antirrechazo, los menores costos que implicaría esta estrategia.…”

Remedy Experience of Severe Abdominal Infection after Orthotopic Liver Transplantation

“…Liver transplant patients are more susceptible to severe abdominal infections than other abdominal surgery patients. Severe abdominal infections after liver transplantation often caused systemic inflammatory response syndrome and cardiopulmonary dysfunction, liver and kidney dysfunction, pyemia, or even septicaemia, which are the most common causes of death in perioperative liver transplantation (3)(4)(5).…”