head JofIMAB
Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski Publishing
ISSN: 1312-773X (Online)
Issue: 2018, vol. 24, issue3
Subject Area: Medicine
DOI: 10.5272/jimab.2018243.2181
Published online: 27 September 2018

Original article

J of IMAB. 2018 Jul-Sep;24(3):2181-2185
Tsvetelina Kostadinova1ORCID logo Corresponding Autoremail, Liliya Ivanova2,3, Ivaylo Hristov4, Tatina Todorova5ORCID logo, Zhivka Stoykova2,3,ORCID logo, Denitsa Tsaneva2ORCID logo,
1) Education and Research Sectors of Medical Laboratory Assistant, Medical College, Medical University, Varna, Bulgaria
2) Department of Microbiology and Virology-Medical University Varna, Bulgaria
3) Laboratory of Clinical Virology-University hospital St. Marina, Varna, Bulgaria
4) Department of Nephrology, Haematology and Gastroenterology, Medical University, Pleven
5) Department of Preclinical and Clinical Sciences, Faculty of Pharmacy, Medical University, Varna, Bulgaria.

Purpose: In Bulgaria, the diagnosis of Epstein-Barr virus (EBV) infection is performed via ELISA testing of IgM and IgG against viral capsid antigen (anti-VCA IgM and anti-VCA IgG). With the current study, we try to answer is there any benefit of determination of IgG against the nuclear antigen of EBV (anti-EBNA-1 IgG) in the laboratory practice.
Material/Methods: The prospective study included 82 serum/plasma samples tested for anti-VCA IgМ, anti-VCA IgG, anti-EBNA1 IgG and anti-VCA IgG avidity in ELISA (Euroimmun, Luebeck, Germany). Quantitative variables were reported as mean, and standard deviation (mean±SD) and the qualitative variables were reported as a number and a relative proportion (%).
Results: Anti-EBNA1 IgG positive patients were 74.4% (95% CI:63.6% - 83.4%) of all tested individuals. Their mean age was significantly higher (30.5;SD±20.5)of this of patients without anti-EBNA1 IgG (14.5; SD±14.1) (p < 0.05).The first group of patients (with infectious mononucleosis, anti-VCA Ig M negative) had the highest number of anti-EBNA1 IgG negative results. Negative for аnti-EBNA 1 IgG were 12% of patients with Hodgkin's lymphoma. Conclusion: Determination of anti-EBNA1 IgG together with anti-VCA should be considered in the initial serological testing in EBV diagnostics. As different immune responses against the EBNA1 antigen exist, clinicians should interpret the results carefully with regard to the clinical symptoms, the immune status and the laboratory markers. We found anti-EBNA1 IgG ELISA tests exceptionally useful to distinguish primary and past infections in anti-VCA IgM(+)/anti-VCA IgG (+) patients.

Keywords: Epstein-Barr virus, anti-EBNA1 IgG, anti-VCA IgG avidity, Infectious mononucleosis, Hodgkin's lymphoma,

pdf - Download FULL TEXT /PDF 550 KB/
Please cite this article as: Kostadinova T, Ivanova L, Hristov I, Todorova T, Stoykova Z, Tsaneva D. The role of anti-EBNA1 IgG determination in EBV diagnostics. J of IMAB. 2018 Jul-Sep;24(3):2181-2185.
DOI: 10.5272/jimab.2018243.2181

Corresponding AutorCorrespondence to: Tsvetelina Kostadinova, MD, PhD. Education and Research Sectors of Medical Laboratory Assistant, Medical College, Medical University – Varna; 84 Tsar Osvoboditel Blvd., Varna, Bulgaria; E-mail: ckostadinova@abv.bg

1. Hess RD. Routine Epstein-Barr virus diagnostics from the laboratory perspective: Still challenging after 35 years. J Clin Microbiol. 2004 Aug;42(8):3381–7. [PubMed] [Crossref]
2. Babcock GJ, Decker LL, Freeman RB, Thorley-Lawson DA. Epstein-barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients. J Exp Med. 1999 Aug 16;190(4):567–76. [PubMed]
3. Hochberg D, Middeldorp JM, Catalina M, Sullivan JL, Luzuriaga K, Thorley-Lawson DA. Demonstration of the Burkitt’s lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo. Proc Natl Acad Sci. 2004 Jan 6;101(1):239–44. [PubMed] [Crossref]
4. Kennedy G, Komano J, Sugden B. Epstein-Barr virus provides a survival factor to Burkitt’s lymphomas. Proc Natl Acad Sci. 2003 Nov 25;100(24):14269–74. [PubMed] [Crossref]
5. Kieff E, Rickinson AB. Epstein –Barr virus and its replicationNo Title. In: Fields Virology. 2007. p. Fields Virology.  
6. Chan KH, Ng MH, Seto WH, Peiris JS. Epstein-Barr virus (EBV) DNA in sera of patients with primary EBV infection. J Clin Microbiol. 2001 Nov 1;39(11):4152–4. [PubMed] [Crossref]
7. Nystad TW, Myrmel H. Prevalence of primary versus reactivated Epstein-Barr virus infection in patients with VCA IgG-, VCA IgM- and EBNA-1-antibodies and suspected infectious mononucleosis. J Clin Virol. 2007 Apr;38(4):292–7. [PubMed] [Crossref]
8. Bauer G. Simplicity through complexity: immunoblot with recombinant antigens as the new gold standard in Epstein-Barr virus serology. Clin Lab. 2001;47(5–6):223–30. [PubMed]
9. Gartner BC, Kortmann K, Schafer M, Mueller-Lantzsch N, Sester U, Kaul H, et al. No correlation in Epstein-Barr virus reactivation between serological parameters and viral load. J Clin Microbiol. 2000 Jun;38(6):2458. [PubMed]
10. De Paschale M, Clerici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions. World J Virol. 2012 Feb 12;1(1):31-43. [PubMed] [Crossref]
11. De Paschale M, Agrappi C, Manco MT, Mirri P, Vigano EF, Clerici P. Seroepidemiology of EBV and interpretation of the "isolated VCA IgG" pattern. J Med Virol. 2009 Feb;81(2):325-31. [PubMed] [Crossref]
12. Teoharov PB. [Study on etiology of viral hepatitis, epidemiology and specific prophylaxis of major hepatotropic viruses and the prevalence of other potentially hepatotropic viruses in Bulgaria.] [dissertation] National Center of Infectious and Parasitic Diseases, Sofia; 2013. 281 p. [in Bulgarian]
13. Henle W, Henle G, Andersson J, Ernberg I, Klein G, Horwitz CA, et al. Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc Natl Acad Sci U S A. 1987 Jan;84(2):570-4. [PubMed]
14. Mueller NE, Lennette ET, Dupnik K, Birmann BM. Antibody titers against EBNA1 and EBNA2 in relation to Hodgkin lymphoma and history of infectious mononucleosis. Int J Cancer. 2012 Jun 15;130(12):2886-91. [PubMed] [Crossref]
15. Levin LI, Chang ET, Ambinder RF, Lennette ET, Rubertone MV, Mann RB, et al. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma. Blood. 2012 Nov 1;120(18):3750-5. [PubMed] [Crossref]
16. Gartner BC, Hess RD, Bandt D, Kruse A, Rethwilm A, Roemer K, et al. Evaluation of four commercially available Epstein-Barr virus enzyme immunoassays with an immunofluorescence assay as the reference method. Clin Diagn Lab Immunol. 2003 Jan;10(1):78–82. [PubMed]
17.  Corrales I, Gimenez E, Navarro D. Evaluation of the Architect Epstein-Barr Virus (EBV) viral capsid antigen (VCA) IgG, VCA IgM, and EBV nuclear antigen 1 IgG chemiluminescent immunoassays for detection of EBV antibodies and categorization of EBV infection status using immunofluorescence assays as the reference method. Clin Vaccine Immunol. 2014 May;21(5):684-8. [PubMed] [Crossref].

Received: 23 May 2018
Published online: 27 September 2018

back to Online Journal