Multicenter comparative study of Epstein-Barr virus DNA quantification for virological monitoring in transplanted patients

J Clin Virol. 2011 Mar;50(3):224-9. doi: 10.1016/j.jcv.2010.12.002. Epub 2010 Dec 24.

Abstract

Background: EBV-related post-transplant lymphoproliferative diseases are usually accompanied by increased EBV DNA in peripheral blood. Monitoring EBV DNAemia is the basis for weighing decisions regarding initiation of pre-emptive or anti-EBV-related tumor therapy. However, the definition of clinically relevant cut-off values is hampered by the lack of standardization in EBV DNA testing.

Objectives: To estimate inter-laboratory variability and to evaluate the impact of different matrices in EBV DNA load determination in Italian laboratories involved in monitoring of virus infections in transplanted patients.

Study design: Two different proficiency panels were distributed among seven centers: the first contained cell-associated and cell-free EBVs; the second was prepared by spiking both cell-associated and cell-free EBVs in EBV DNA-negative whole blood from EBV seropositive healthy donors. Samples were extracted and amplified with different methods. Intra-laboratory and inter-laboratory variabilities was evaluated.

Results: 337 EBV DNA determinations were performed. Sensitivity was 100% for both panels, specificity was 100% for the first and 74% for the second panel, where whole blood was utilized as the matrix. Discrepant results in the second panel were restricted to samples containing low copy numbers. Quantification fell within ±0.5 log in 73% of the determinations. Values for cell-associated samples tended to be more heterogeneous than those obtained from cell-free samples. Good overall linearity was observed for each sample type; inter-laboratory variability ranged from 4.71% to 12.86%.

Conclusions: The results of this multicenter study indicate that EBV DNAemia may be reliably quantified by different laboratories using a variety of commercial and in-house molecular assays.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood / virology
  • DNA, Viral / isolation & purification*
  • Epstein-Barr Virus Infections / diagnosis*
  • Epstein-Barr Virus Infections / virology
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Italy
  • Reproducibility of Results
  • Transplantation*
  • Viral Load / methods*
  • Viral Load / standards*

Substances

  • DNA, Viral