Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders

Rev Argent Microbiol. 2016 Apr-Jun;48(2):110-8. doi: 10.1016/j.ram.2016.02.006. Epub 2016 May 4.

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.

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.

MeSH terms

  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • DNA, Viral / blood
  • Early Detection of Cancer
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / virology*
  • Follow-Up Studies
  • Heart Transplantation*
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Immunocompromised Host
  • Infant
  • Kidney Transplantation*
  • Leukocytes, Mononuclear / virology
  • Liver Transplantation*
  • Lymphoid Tissue / virology
  • Lymphoma / diagnosis
  • Lymphoma / etiology
  • Lymphoma / virology
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / virology*
  • Postoperative Complications / diagnosis
  • Postoperative Complications / etiology
  • Postoperative Complications / virology*
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Viral Load
  • Viremia / diagnosis*

Substances

  • DNA, Viral