Epstein-Barr Virus (EBV) Serology Screen Antibody Profile


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Subject: Epstein-Barr Virus (EBV) Serology Screen Antibody Profile

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  • EBV is the etiologic agent of infectious mononucleosis (IM) and is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and EBV shedders. EBV spreads primarily via passage of saliva but is not a particularly contagious disease. The virus can persist in the oropharynx of patients with IM for up to 18 months following clinical recovery. EBV has also been isolated in both cervical epithelial cells and in male seminal fluid, suggesting that transmission may also occur sexually. This test comprises four serologic markers: EBV-NA (nuclear antigen IgG); EBV-VCA (viral capsid antigen) IgG and IgM; infectious mononucleosis antibody; and EBV-EA IgG (early antigen IgG).

  • Normal range: Negative.

  • Tests for EBV:

    • IgG-VCA: Indicates past infection and immunity. May be present early in illness, usually before clinical symptoms are present. Detected at onset in 100% of cases; only 20% show a fourfold increase in titer after visiting a physician. Decreases during convalescence but detectable for many years after illness; therefore, not helpful in establishing diagnosis of IM.

    • IgM-VCA: Detected at onset in 100% of cases; high titers present in serum 1–6 weeks after onset of illness, starts to fall by 3rd week and usually disappear in 1–6 months. Sera are often taken too late to be detected. It is almost always present in active EBV infection and, thus, most sensitive and specific to confirm acute IM. May be positive in other herpes virus infections (especially CMV); therefore, confirmation with IgG and EBV-NA assays is recommended.

    • Early antigen: IgG antibodies to early antigen are present at the onset of clinical illness. There are two subsets of EA IgG: anti-D and anti-R. The presence of anti-D antibodies is consistent with recent infection, since titers disappear after recovery; however, their absence does not exclude acute illness because the antibodies are not expressed in a significant number of patients. Anti-R antibodies are only occasionally present in IM.

    • Early antigen anti-D titers rise later (3–4 weeks after onset; is transient) in course of IM than AB-VCA and disappear with recovery; combined with IgG-VCA suggests recent EBV infection; only found in 70% of patients with IM due to EBV. High titers are found in nasopharyngeal carcinoma due to EBV. Early antigen anti-R antibodies occur rarely in primary EBV infection, 2 weeks to months after onset, and may persist for a year; more often in atypical or protracted cases. No clinical significance; high titers are found in chronic active EBV infection or Burkitt lymphoma.

    • Epstein-Barr nuclear antigen: Last antibodies to appear and are rare in acute phase; develops 4–6 weeks after onset of clinical illness and rises during convalescence (3–12 months) and persists for many years after illness. Absence when IgM-VCA and anti-D are present implies recent infection. Appearance early in illness excludes primary EBV infection. Appearance after previous negative test evidences recent EBV infection.


  • Diagnosing IM. In patients with suspected IM and a negative heterophile test.


Table 17-1
Table 17–1
Interpretation of Epstein-Barr Virus (EBV) Serologic Status


  • EBV serology testing should not be performed as a screening procedure for the general population. The predictive value of a positive or negative result depends on the prevalence of analyte in a given patient population. Testing should only be done when clinical evidence suggests the diagnosis of EBV-associated infectious mononucleosis.

  • Antibodies to EBV have been demonstrated in all population groups with a worldwide distribution; approximately 90–95% of adults are eventually EBV seropositive. EBV acquired during childhood years is often subclinical; <10% of children develop clinical infection despite the high rates of exposure.

  • The false-negative rates are highest during the beginning of clinical symptoms (25% in the first week; 5–10% in the 2nd week, 5% in the 3rd week).

  • Approximately 10% of mononucleosis-like cases are not caused by EBV. Other agents that produce a similar clinical syndrome include CMV, HIV, toxoplasmosis, HHV-6, hepatitis B, and possibly HHV-7.

  • IgM and IgG antibodies directed against viral capsid antigen have high sensitivity and specificity for the diagnosis of IM (97% and 94%, respectively).