Programmed Death–1 Expression in Liver Transplant Recipients as a Prognostic Indicator of Cytomegalovirus Disease

Abstract

Immunological parameters that distinguish solid-organ transplant (SOT) recipients at risk for life-threatening cytomegalovirus (CMV) disease are being actively pursued to aid posttransplant management. A candidate marker is programmed death (PD)-1 receptor, whose overexpression has been associated with disease progression during persistent viral infections. To determine whether levels of this negative regulator of T cell activity are altered in SOT recipients with symptoms of CMV disease, a comparative PD-1 expression analysis was done in healthy, CMV-positive individuals and in liver transplant recipients. PD-1 levels were measured among the total population of CD8(+) and CD8(+) T cells binding to CMV-specific major histocompatibility complex class I tetramers. Minimal PD-1 expression was found in the healthy, CMV-positive cohort, and symptomatic SOT recipients had significantly higher PD-1 levels. PD-1 up-regulation was significantly associated with incipient and overt CMV disease and with viremia. Our findings suggest that PD-1 could be developed as a prognostic tool to predict CMV disease and guide therapeutic interventions.

Current concepts on cytomegalovirus infection after liver transplantation

“…In one study, programmed death1 recep tor upregulation was significantly associated with incipient and overt CMV disease and with CMV viremia [48] .…”

“…Other immune measures, such as programmed dea th1 expression [48] , mannose binding lectin levels or gene mutation, and immune evasion genes [49] have also been assessed as prognostic indicators of CMV disease after transplantation. In one study, programmed death1 recep tor upregulation was significantly associated with incipient and overt CMV disease and with CMV viremia [48] .…”

Cytomegalovirus infection after liver transplantation: Current concepts and challenges

“…In one study, programmed death-1 receptor up-regulation was significantly associated with incipient and overt CMV disease and with CMV viremia [42] .…”

“…Table 3 Selected traditional and novel factors associated with the increased risk of CMV disease after liver transplantation 1 Others factors include re-transplantation, volume of blood transfusion, sepsis and factors associated with high tumor necrosis factor-α secretion [1,4,11,13,21,[39][40][41][42]77,[89][90][91][92][93] .…”

“…Other immune measures, such as programmed death-1 expression [42] and immune evasion genes [43] have also been assessed as prognostic indicators of CMV disease after liver transplantation. In one study, programmed death-1 receptor up-regulation was significantly associated with incipient and overt CMV disease and with CMV viremia [42] .…”