Immunologic and virologic analyses in pediatric liver transplant recipients with chronic high Epstein-Barr virus loads

J Infect Dis. 2010 Aug 15;202(3):461-9. doi: 10.1086/653737.

Abstract

Background: Long-term Epstein-Barr virus (EBV) monitoring for potentially life-threatening posttransplant lymphoproliferative disorder (PTLD) has identified asymptomatic patients who maintain high EBV loads over long periods.

Methods: Thirty-one pediatric liver transplant recipients were designated as 11 chronic high EBV load carriers (EBV DNA level >5000 copies/mL of whole blood for >6 months) and 20 control recipients. Serial quantification of EBV DNA, measurement of interleukin 10 (IL-10) concentrations, EBV-specific tetramer staining, and relative quantification of EBV gene expression in peripheral blood mononuclear cells were performed.

Results: Most of the chronic high EBV load carriers were seronegative at transplant, the median time to resolution of a chronic high EBV load was 23 months, and no recipient developed late-onset PTLD. EBV DNA was detected predominantly in CD19(+) cells. The plasma concentration of IL-10 and the EBV-specific CD8(+) cell frequency did not differ significantly between the chronic high EBV load carriers and the control recipients. Analysis of gene expression showed that EBV-encoded small RNA 1, BamHI A rightward transcripts, and latent membrane protein 2 were positive in peripheral blood mononuclear cells from chronic high EBV load carriers.

Conclusions: EBV-infected cells in the blood of chronic high EBV load carriers expressed a highly restricted set of latency genes, suggesting that the EBV-infected cells escaped from a T cell response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19 / analysis
  • CD8-Positive T-Lymphocytes / immunology
  • Child, Preschool
  • DNA, Viral / blood
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Gene Expression Profiling
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Infant
  • Interleukin-10 / blood
  • Leukocytes, Mononuclear / chemistry
  • Leukocytes, Mononuclear / virology
  • Liver Transplantation*
  • Male
  • Transplantation
  • Viral Load*
  • Viral Proteins / biosynthesis

Substances

  • Antigens, CD19
  • DNA, Viral
  • Viral Proteins
  • Interleukin-10