title: Multicenter Evaluation of Whole-Blood Epstein-Barr Viral Load Standardization Using the WHO International Standard.
abstract: The first WHO international standard for Epstein-Barr virus (EBV) (WHO EBV standard) for nucleic acid amplification technology (NAT)-based assays was commercialized in January 2012 by the National Institute for Biological Standards and Control. In the study reported here, we compared whole-blood EBV DNA load (EDL) results from 12 French laboratories for seven samples (Quality Controls for Molecular Diagnostics 2013 proficiency panel) in order to determine whether expression in international units reduces interlaboratory variability in whole-blood EDLs. Each testing laboratory used a conversion factor to convert EDL results from copies per milliliter to international units per milliliter. This conversion factor was calculated from the WHO EBV standard according to the protocol described in this study (nine laboratories) or the recommendations of the PCR kit suppliers (three laboratories). The interlaboratory variability in whole-blood EDL results was reduced after standardization of the results using the WHO EBV standard. For the seven samples tested, standard deviations (SD) ranged from 0.41 to 0.55 when the results were expressed in log copies per milliliter, whereas the SD ranged from 0.17 to 0.32 when results were given in log international units per milliliter. Comparing the variance data (F test), we showed that the dispersion of whole-blood EDL results was significantly lower when they were expressed in log international units per milliliter (P < 0.001 for six of seven samples and P < 0.05 for one sample with a low mean EDL of 2.62 log IU/ml). This study showed that the use of the WHO EBV standard could improve the homogeneity of whole-blood EDL results between laboratories as well as the monitoring of patients at high risk of posttransplant lymphoproliferative disorders or other EBV-associated diseases.
authors.affiliation: IBS, UMR 5075 CEA-CNRS-Université Grenoble-Alpes, Grenoble, France.|Department of Virology, Grenoble University Hospital, Université Grenoble-Alpes, Grenoble, France.
authors.forename: Touyana
authors.initials: T
authors.lastname: Semenova
authors.affiliation: IBS, UMR 5075 CEA-CNRS-Université Grenoble-Alpes, Grenoble, France.|Department of Virology, Grenoble University Hospital, Université Grenoble-Alpes, Grenoble, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lupo
authors.affiliation: Department of Virology, French National Cytomegalovirus Reference Center, Limoges University Hospital, Limoges, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Alain
authors.affiliation: Department of Virology, Grenoble University Hospital, Université Grenoble-Alpes, Grenoble, France.
authors.forename: Gwladys
authors.initials: G
authors.lastname: Perrin-Confort
authors.affiliation: IBS, UMR 5075 CEA-CNRS-Université Grenoble-Alpes, Grenoble, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Grossi
authors.affiliation: IBS, UMR 5075 CEA-CNRS-Université Grenoble-Alpes, Grenoble, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dimier
authors.affiliation: IBS, UMR 5075 CEA-CNRS-Université Grenoble-Alpes, Grenoble, France.|Department of Infectious Diseases, Grenoble University Hospital, Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Epaulard
authors.affiliation: IBS, UMR 5075 CEA-CNRS-Université Grenoble-Alpes, Grenoble, France.|Department of Virology, Grenoble University Hospital, Université Grenoble-Alpes, Grenoble, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Morand
authors.affiliation: IBS, UMR 5075 CEA-CNRS-Université Grenoble-Alpes, Grenoble, France RGermi@chu-grenoble.fr.|Department of Virology, Grenoble University Hospital, Université Grenoble-Alpes, Grenoble, France.
authors.forename: Raphaële
authors.initials: R
authors.lastname: Germi
mesh_terms: D001769:Blood / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D005602:France; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D021141:Nucleic Acid Amplification Techniques / Q000379:methods / Q000592:standards*; D012015:Reference Standards; D015203:Reproducibility of Results; D019562:Viral Load / Q000379:methods / Q000592:standards*; D014944:World Health Organization