title: Effective control of Epstein-Barr virus infection following pediatric liver transplantation by monitoring of viral DNA load and lymphocyte surface markers.
abstract: EBV-associated PTLD is a serious complication of liver transplantation. We performed periodical molecular EBV monitoring in 140 consecutive pediatric patients who had living-related liver transplantation in the National Center for Child Health and Development, Tokyo. Sixty-three of the 140 patients showed elevation of EBV DNA level to >10(2) copies/μg DNA and were further examined immunologically by flow cytometry, and the dose of tacrolimus and/or cyclosporine A was adjusted according to the results. The decrease in CD4/CD8 ratio and the increase in the number of HLA-DR(+) CD8(+) cells were observed in parallel with the decrease in EBV DNA load and in the number of CD19(+) CD23(+) cells following the reduction in immunosuppressive drugs. Analysis with HLA tetramers in a patient demonstrated a dramatic increase in the number of CD8(+) T cells specific to the EBV latent protein LMP2 accompanying the decline of EBV DNA load, suggesting that T cells of this specificity were actually involved in the control of EBV infection. No clinically apparent PTLD has developed in the 140 recipients, suggesting that our program of EBV control by molecular EBV monitoring coupled with lymphocyte phenotype analyses is effective in controlling EBV infection in pediatric liver transplant recipients.
authors: Department of Infectious Diseases, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan. imadome@nch.go.jp
authors: Ken-ichi
authors: K
authors: Imadome
authors: Akinari
authors: A
authors: Fukuda
authors: Fuyuko
authors: F
authors: Kawano
authors: Yumi
authors: Y
authors: Imai
authors: Sayumi
authors: S
authors: Ichikawa
authors: Masashi
authors: M
authors: Mochizuki
authors: Takanobu
authors: T
authors: Shigeta
authors: Toshihiko
authors: T
authors: Kakiuchi
authors: Seisuke
authors: S
authors: Sakamoto
authors: Mureo
authors: M
authors: Kasahara
authors: Shigeyoshi
authors: S
authors: Fujiwara
mesh_terms: D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D004279:DNA, Viral / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000209:etiology* / Q000517:prevention & control*; D005434:Flow Cytometry / Q000379:methods; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017093:Liver Failure / Q000150:complications* / Q000628:therapy; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D008214:Lymphocytes / Q000821:virology*; D017455:Receptors, IgE / Q000096:biosynthesis; D016559:Tacrolimus / Q000627:therapeutic use; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D017455:Receptors, IgE; D014763:Viral Matrix Proteins; D016572:Cyclosporine; D016559:Tacrolimus