title: Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders.
abstract: High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed.
authors.affiliation: Oncogenic Viruses Service, Virology Department, "Carlos G. Malbrán" National Institute of Infectious Diseases, Av. Vélez Sársfield 563, C1282AFF Buenos Aires, Argentina. Electronic address: oncovir1@anlis.gov.ar.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Fellner
authors.affiliation: Oncogenic Viruses Service, Virology Department, "Carlos G. Malbrán" National Institute of Infectious Diseases, Av. Vélez Sársfield 563, C1282AFF Buenos Aires, Argentina.
authors.forename: Karina A
authors.initials: KA
authors.lastname: Durand
authors.affiliation: Pathology Service, "Prof. Dr. Juan. P. Garrahan" National Pediatrics Hospital, Pichincha 1890, C1249ABP Buenos Aires, Argentina.
authors.forename: Veronica
authors.initials: V
authors.lastname: Solernou
authors.affiliation: Pathology Service, "Prof. Dr. Juan. P. Garrahan" National Pediatrics Hospital, Pichincha 1890, C1249ABP Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bosaleh
authors.affiliation: Pathology Service, "Prof. Dr. Juan. P. Garrahan" National Pediatrics Hospital, Pichincha 1890, C1249ABP Buenos Aires, Argentina.
authors.forename: Ziomara
authors.initials: Z
authors.lastname: Balbarrey
authors.affiliation: Pathology Service, "Prof. Dr. Juan. P. Garrahan" National Pediatrics Hospital, Pichincha 1890, C1249ABP Buenos Aires, Argentina.
authors.forename: María T
authors.initials: MT
authors.lastname: García de Dávila
authors.affiliation: Operational Team Quality Management, Parasitology Department, "Carlos G. Malbrán" National Institute of Infectious Diseases, Av. Vélez Sársfield 563, C1282AFF Buenos Aires, Argentina.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rodríguez
authors.affiliation: Operational Team Quality Management, Parasitology Department, "Carlos G. Malbrán" National Institute of Infectious Diseases, Av. Vélez Sársfield 563, C1282AFF Buenos Aires, Argentina.
authors.forename: Lucía
authors.initials: L
authors.lastname: Irazu
authors.affiliation: Oncogenic Viruses Service, Virology Department, "Carlos G. Malbrán" National Institute of Infectious Diseases, Av. Vélez Sársfield 563, C1282AFF Buenos Aires, Argentina.
authors.forename: Lidia V
authors.initials: LV
authors.lastname: Alonio
authors.affiliation: Oncogenic Viruses Service, Virology Department, "Carlos G. Malbrán" National Institute of Infectious Diseases, Av. Vélez Sársfield 563, C1282AFF Buenos Aires, Argentina.
authors.forename: María A
authors.initials: MA
authors.lastname: Picconi
mesh_terms: D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood; D055088:Early Detection of Cancer; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000821:virology*; D005500:Follow-Up Studies; D016027:Heart Transplantation; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000821:virology; D016031:Liver Transplantation; D008221:Lymphoid Tissue / Q000821:virology; D008223:Lymphoma / Q000175:diagnosis / Q000209:etiology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000209:etiology / Q000821:virology*; D011183:Postoperative Complications / Q000175:diagnosis / Q000209:etiology / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis*
chemical_list: D004279:DNA, Viral
keywords: Carga viral; Detección temprana de PTLD; Early PTLD detection; Epstein–Barr virus; Linfoma; Lymphoma; PCR en tiempo real; Pacientes trasplantados; Real-time PCR; Transplant patients; Viral load; Virus Epstein-Barr