Pretransplant immediately early-1-specific T cell responses provide protection for CMV infection after kidney transplantation

Am J Transplant. 2013 Jul;13(7):1793-805. doi: 10.1111/ajt.12256. Epub 2013 May 24.

Abstract

Cytomegalovirus (CMV) infection is still a major complication after kidney transplantation. Although cytotoxic CMV-specific T cells play a crucial role controlling CMV survival and replication, current pretransplant risk assessment for CMV infection is only based on donor/recipient (IgG)-serostatus. Here, we evaluated the usefulness of monitoring pre- and 6-month CMV-specific T cell responses against two dominant CMV antigens (IE-1 and pp65) and a CMV lysate, using an IFN-γ Elispot, for predicting the advent of CMV infection in two cohorts of 137 kidney transplant recipients either receiving routine prophylaxis (n = 39) or preemptive treatment (n = 98). Incidence of CMV antigenemia/disease within the prophylaxis and preemptive group was 28%/20% and 22%/12%, respectively. Patients developing CMV infection showed significantly lower anti-IE-1-specific T cell responses than those that did not in both groups (p < 0.05). In a ROC curve analysis, low pretransplant anti-IE-1-specific T cell responses predicted the risk of both primary and late-onset CMV infection with high sensitivity and specificity (AUC > 0.70). Furthermore, when using most sensitive and specific Elispot cut-off values, a higher than 80% and 90% sensitivity and negative predictive value was obtained, respectively. Monitoring IE-1-specific T cell responses before transplantation may be useful for predicting posttransplant risk of CMV infection, thus potentially guiding decision-making regarding CMV preventive treatment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / blood
  • Antigens, Viral / immunology
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / prevention & control
  • Female
  • Follow-Up Studies
  • Graft Survival / immunology*
  • Humans
  • Immediate-Early Proteins / immunology*
  • Immediate-Early Proteins / metabolism
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Preoperative Period
  • Prognosis
  • Retrospective Studies
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • Antigens, Viral
  • Antiviral Agents
  • Immediate-Early Proteins