Evidence-Based Approach for Interpretation of Epstein-Barr Virus Serological Patterns

Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Journal of clinical microbiology (Impact Factor: 4.23). 08/2009; 47(10):3204-10. DOI: 10.1128/JCM.00164-09
Source: PubMed

ABSTRACT Diagnosis of Epstein-Barr virus (EBV) infection is based on clinical symptoms and serological markers, including the following: immunoglobulin G (IgG) and IgM antibodies to the viral capsid antigen (VCA), heterophile antibodies, and IgG antibodies to the EBV early antigen-diffuse (EA-D) and nuclear antigen (EBNA-1). The use of all five markers results in 32 possible serological patterns. As a result, interpretation of EBV serologies remains a challenge. The purpose of this study was to use a large population of patients to develop evidence-based tools for interpreting EBV results. This study utilized 1,846 serum specimens sent to the laboratory for physician-ordered EBV testing. Chart review was performed for more than 800 patients, and diagnoses were assigned based on physician-ordered testing, clinical presentation, and patient history. Testing for all five EBV antibodies was performed separately on all serum samples using the Bio-Rad BioPlex 2200 system. Presumed EBV diagnosis (based on previous publications) was compared to EBV diagnosis based on a medical record review for each serological pattern. Interestingly, of the 32 possible serological patterns, only 12 occurred in > or = 10 patients. The remaining 20 patterns were uninterpretable because they occurred with such infrequency. Two easy-to-use tables were created to interpret EBV serological patterns based on whether three (EBV VCA IgG, IgM, and heterophile) or five markers are utilized. The use of these two tables allows for interpretation of >95% of BioPlex serological results. This is the first evidence-based study of its kind for EBV serology.

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Available from: Bradley A Ford, Dec 31, 2014
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    • "In humans, infection with EBV is marked by an early and persistent IgG antibody response directed against the highly immunogenic, lytic phase small VCAs p18 and p23 (van Grunsven et al., 1993a; Hinderer et al., 1999). IgG titers against these lytic antigens are extremely robust, minimally affected by immune suppression and persist for the lifetime of the individual (Klutts et al., 2009). As such, their identification is used routinely to confirm infection with EBV in humans (reviewed in Pattle and Farrell, 2006). "
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    ABSTRACT: In humans, chronic infection with the gammaherpesvirus Epstein-Barr virus is usually asymptomatic; however some infected individuals develop hematological and epithelial malignancies. The exact role of EBV in lymphomagenesis is poorly understood partly because of the lack of clinically relevant animal models. Here we report the detection of serological responses against EBV capsid antigens in healthy dogs and dogs with spontaneous lymphoma and that dogs with the highest antibody titers have B cell lymphoma. Moreover, we demonstrate the presence of EBV-like viral DNA and RNA sequences and Latent Membrane Protein-1 in malignant lymph nodes of dogs with lymphoma. Finally, electron microscopy of canine malignant B cells revealed the presence of classic herpesvirus particles. These findings suggest that dogs can be naturally infected with an EBV-like gammaherpesvirus that may contribute to lymphomagenesis and that dogs might represent a spontaneous model to investigate environmental and genetic factors that influence gammaherpesvirus-associated lymphomagenesis in humans.
    Virology 03/2012; 427(2):107-17. DOI:10.1016/j.virol.2012.02.013 · 3.28 Impact Factor
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    • ". A recent study showed a pattern of VCA IgG positive and VCA IgM, EBNA-1 IgG, and anti-EA(D) IgG negative (and heterophile antibody negative) as associated with past infection, while a pattern of VCA IgG and anti-EA(D) IgG positive but VCA IgM and EBNA-1 IgG negative has a still unclear meaning [20]. "
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    ABSTRACT: The presence of an “isolated viral capsid antigen (VCA) IgG” pattern in serum is not easy to interpret without the aid of further tests, such as specific immunoblotting or a virus genome search, that often give rise to organisational and economic problems. However, one alternative is to use an enzyme-linked immunosorbent assay (ELISA) to detect anti-early antigen (EA) antibodies, which can be found in about 85% of subjects with acute Epstein-Barr virus (EBV) infections. The purpose of this work was to search for anti-EA(D) antibodies in 130 samples with an isolated VCA IgG pattern at ELISA screening and classified as being indicative of past (102 cases) or acute (28 cases) infection on the basis of the immunoblotting results. Thirty-seven samples (28.5%) were positive for anti-EA(D), of which 25 (89.3%) had been classified by immunoblotting as indicating acute and 12 (11.8%) past EBV infection. This difference was statistically significant (P < .01). The results of our search for anti-EA(D) antibodies correctly identified nearly 90% of acute (presence) or past EBV infections (absence). When other tests are not available, the search for anti-EA antibodies may therefore be helpful in diagnosing patients with an isolated VCA IgG pattern at screening tests.
    International Journal of Microbiology 06/2010; 2010:695104. DOI:10.1155/2010/695104
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    ABSTRACT: Epstein-Barr virus (EBV) is a gammaherpesvirus that infects a large fraction of the human population. Primary infection is often asymptomatic but results in lifelong infection, which is kept in check by the host immune system. In some cases, primary infection can result in infectious mononucleosis. Furthermore, when host-virus balance is not achieved, the virus can drive potentially lethal lymphoproliferation and lymphomagenesis. In this review, we describe the biology of EBV and the host immune response. We review the diagnosis of EBV infection and discuss the characteristics and pathogenesis of infectious mononucleosis. These topics are approached in the context of developing therapeutic and preventative strategies.
    Clinical microbiology reviews 01/2011; 24(1):193-209. DOI:10.1128/CMR.00044-10 · 16.00 Impact Factor
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