Virology Laboratory

Epstein-Barr Virus (EBV) serology panel - serum specimen

  • LIS Mnemonic: IEBV

    Collect

    Gold (SST - Clot activator & gel)

    Volume Required

    2 ml blood

    Minimum Required

    1 ml serum

    Transport

    Room temperature

    Processing

    If multiple viral serologies are being requested from the same specimen, the general rule is to collect a total of 2-4 ml of blood for every 2-3 tests ordered. If sending specimens as an outside client, remove the serum from the clotted blood before transporting to the laboratory. The serum should be refrigerated after collection and transported to the laboratory at refrigerated temperatures (4°C). If an extended delay in transport of specimens is anticipated, rapidly freeze the specimens to at least -60°C and transport to the laboratory on dry ice. A single serum specimen is required for EBV antibody testing.

Days Performed

Monday, Wednesday, and Friday

Reported

Same day

Reflex Testing

N/A

CPT

86663,86664,86665

Methodology

Immunofluorescence. The panel of tests includes titration of IgG and IgM antibodies to the Viral Capsid Antigen (VCA), IgG antibodies to Diffuse (D) and Restricted (R) Early Antigens (EA), and IgG antibodies to Nuclear Antigens (EBNA) of EBV.

Interpretation

In most patients with acute EBV infection, high titers of both IgG and IgM to EBV viral capsid antigen (VCA) are detectable. Measurable IgG to VCA then persists for life, while IgM to VCA usually declines to undetectable levels within 2-4 months. IgG antibody to EBV early antigen (EA) rises during acute infection, then declines within 3-6 months. IgG antibodies to EBNA are normally not detected or are observed at very low titers (e.g., 1:2) during acute EBV disease and elevate to higher levels with time as a patient progresses to convalescence. IgG antibodies to EBNA then persist for life. Unusually high IgG antibody responses to VCA and EA in the presence of IgG antibody against EBNA is indicative of reactivated EBV infection. Of note, in some patients, a low positive IgM to VCA may persist for many months to a year or more following acute infection or may be positive during reactivated infection. A false positive reaction with IgM can occur in the presence of rheumatoid factor. Lastly, low or transient levels of antibody to EA can also be detected in otherwise healthy individuals for years after EBV infection.

Reference Values

VCA (Viral Capsid Antigen) IgG <1:40 (not detected)
VCA (Viral Capsid Antigen) IgM <1:10 (not detected)
EA (Early Antigen IgG <1:10 (not detected)
EBNA (Nuclear Antigen) IgG <1:2 (not detected)

Remarks

Clinical Utility: EBV is the primary cause of infectious mononucleosis (IM). Infections with EBV can lead to hepatitis, pneumonia, myocarditis, neurologic syndromes, hemolytic anemia, thrombocytopenia, and hemophagocyctic syndrome. The virus is also associated with posttransplantation lymphoproliferative disorders (PTLD), Burkitt lymphoma, X-linked lymphoproliferative syndrome, nasopharyngeal carcinoma, and lymphomas of the CNS. For patients with acute IM, the detection of heterophile antibodies is diagnostic. For patients with heterophile-negative IM or other illnesses compatible with EBV infection, EBV-specific serological tests should be performed. Interpretations of the EBV serology panel permit identification of current or recent primary EBV infection, past infections, recurrent or chronic EBV illness, as well as Burkitt's lymphoma, nasopharyngeal carcinoma, and other EBV-associated lymphomas. The EBV-specific comprehensive antibody panel should be routinely used in the setting of heterophile antibody-negative IM and in all children 4 years of age or less since they often do not produce an adequate heterophile antibody response. Only a single, acute-phase serum sample is needed since antibody titers to EBV appear rapidly during primary infections and most patients have peak titers when they are first seen by a physician. NOTE: The diagnosis of EBV infection is increasingly being made by PCR, so consider this test as well when ordering EBV serologies. Refer to the Online Service Directory for more details regarding real-time PCR assays for EBV and their clinical utility.

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