Immunologic and virologic analyses in pediatric liver transplant recipients with chronic high Epstein-Barr virus loads.
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.
Gotoh
Kensei
K
Department of Pediatrics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Ito
Yoshinori
Y
Ohta
Rieko
R
Iwata
Seiko
S
Nishiyama
Yukihiro
Y
Nakamura
Taro
T
Kaneko
Kenitiro
K
Kiuchi
Tetsuya
T
Ando
Hisami
H
Kimura
Hiroshi
H
D018941:Antigens, CD19 / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D014180:Transplantation; D019562:Viral Load; D014764:Viral Proteins / Q000096:biosynthesis
D018941:Antigens, CD19; D004279:DNA, Viral; D014764:Viral Proteins; D016753:Interleukin-10