Immunologic and virologic analyses in pediatric liver transplant recipients with chronic high epstein-barr virus loads

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 15000 copies/mL of whole blood for 16 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. © 2010 by the Infectious Diseases Society of America.