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: 3.99). 08/2009; 47(10):3204-10. DOI: 10.1128/JCM.00164-09
Source: PubMed


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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    • "Exposure to EBV predominantly occurs in early adulthood. EBV may cause a number of clinical syndromes, including acute mononucleosis and has been associated with a variety of malignancies, including B-cell and T-cell lymphoma [2]. Acute primary infection with EBV is mostly characterized by transient fever, lymphadenopathy and may cause a transient hepatosplenomegaly. "
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    ABSTRACT: Introduction Hodgkin’s disease is highly curable by radiotherapy and/or chemotherapy, but refractory disease or early relapses are rarely cured by conventional salvage therapy. Case presentation We report a case of a 20-year-old Caucasian man, with a biopsy-proven intrapulmonary relapse of Hodgkin’s disease, for whom salvage chemotherapy was administered. During salvage chemotherapy intense increased F18-fluorodeoxyglucose uptake was noticed in multiple lymph nodes and diffuse increased splenic uptake, suggesting chemotherapy-refractory disease. However, additional information obtained from the patient revealed he recently had met his first girlfriend. An asymptomatic primary Epstein–Barr virus infection was considered proven. Conclusions Interim F18-fluorodeoxyglucose-positron emission tomography/computed tomography is a strong prognostic factor for advanced Hodgkin’s and may better identify those patients needing intensified chemotherapy. Related to the nonspecificity of F18-fluorodeoxyglucose, clinical awareness of the potential interference of intercurrent asymptomatic viral infections with treatment and remission status monitoring continues to be important in the interpretation of equivocal medical imaging results.
    Full-text · Article · Jun 2014 · Journal of Medical Case Reports
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    • "IgG antibodies to the EBV VCA may be detected a few weeks or months after the onset of infection, and can persist for life [9]. In addition, IgG antibodies to the EBV early diffuse antigen (EA) can also be detected during acute infections [18,19]. Antibodies to the Epstein-Barr nuclear antigen (EBNA) indicate the presence of a past infection. "
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    ABSTRACT: Background Many natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection. Material and Methods The data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection. Results Our data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels. Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease. In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D. Conclusions The clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.
    Full-text · Article · May 2014 · Medical science monitor: international medical journal of experimental and clinical research
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    • "In a study by Nystad et al., the simultaneous detection of VCA IgM, VCA IgG and EBNA-1 was associated with primary infection in 42% of their patients, although in at least 23% of the study group it was associated with clinically inconsequential EBV reactivation [18]. In contrast, Klutts et al. found that 77.8% of patients who were VCA IgM+/VCA IgG+/EBNA-1+ proved to have had a past infection, were recovering from a primary infection, or were manifesting EBV reactivation [9]. Debyser et al. also associated the triple-positive serotype with reactivation, noting that reactivation can also be indicated by the VCA IgM+/VCA IgG–/EBNA-1+ serotype, but proposed that reactivation is only relevant in patients suffering from (or as in the case with Garcia et al., [17] subject to) immune suppression. "
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    ABSTRACT: Background Diagnosis of Epstein–Barr virus (EBV) infection is routinely conducted by clinical laboratories, especially to diagnose infectious mononucleosis. At an estimated general population incidence of 1:200, this represents a potentially significant testing burden. We evaluated the reliability of the Siemens Novagnost® and Enzygnost® EBV microtiter assays measuring VCA IgM and IgG, and EBNA-1 IgG for clinical diagnosis of EBV-related infectious mononucleosis. Methods Remnant sera from 537 patients tested for EBV infection were used to compare the Siemens assays to each other and to the Merifluor assay. The Siemens assays are qualitative/semiquantitative, automatable enzyme immunoassays. The Merifluor assays are manual, qualitative indirect immunofluorescent assays. Testing was conducted on the Siemens and Merifluor assays in parallel. All assays were conducted and interpreted according to each manufacturer’s specifications. Agreement of serostatus between each of the three assays was assessed. Discrepant results were resolved using a third method (Mikrogen recomLine). Results Final EBV serostatus indicated 2.9% of the population had an acute infection, 89.6% had a past infection, and 7.5% were EBV naive. All three assays demonstrated 100% agreement with acute infection. Agreement with past-infection serostatus was 99.1% for Enzygnost, between 86% and 98.8% for Novagnost, and 98.1% for Merifluor. Seronegative agreement was 100% for Enzygnost, 89.7% for Novagnost, and 92.3% for Merifluor. Conclusions The Siemens Enzygnost and Novagnost EBV microtiter assays are suitable for clinical rule-in of acute EBV infection and for identifying EBV-naive individuals. Both assays also adequately identify remote EBV infections. Because these assays can be automated, they can improve speed and efficiency of EBV testing, especially in high-volume laboratories.
    Full-text · Article · Jun 2013 · BMC Infectious Diseases
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