Type of test Blood

Normal findings

 VCA-IgM: Negative < 36 U/mL, Equivocal 36-43.9 U/mL, Positive > 43.9 U/mL

VCA-IgG: Negative < 18 U/mL, Equivocal 18-21.9 U/mL, Positive > 21.0 U/mL

EBNA-IgG: Negative < 18 U/mL, Equivocal 18-21.9 U/mL, Positive > 21.9 U/mL

EA-IgG: Negative < 9 U/mL, Equivocal 9-10.9 U/mL, Positive > 10.9 U/mL

For accuracy, check the normal values of the lab performing the test.

Test explanation and related physiology

 EBV is a herpesvirus (human herpes virus 4) that affects 90%-95% of adults worldwide. It is the primary cause of infectious mononucleosis and has a latency phase that persists for life in most adults. In some people, it is associated with the development of B-cell lymphomas, T-cell lymphomas, Hodgkin lymphoma, and nasopharyngeal carcinomas. Laboratory findings of lymphocytosis and atypical lymphocytes support the diagnosis of acute EBV, but it should be confirmed with a heterophile antibody test or through EBV-specific antibodies.

The majority of EBV infections can be diagnosed by solely testing the patient’s serum for heterophile antibodies (rapid latex slide agglutination test or mononucleosis [mono] spot test). This test can result in a false negative in early infection and in children younger than 4 years of age. Also, immunosuppressed patients may have serologic negative tests.

EBV-specific antibodies can be used in a patient when the heterophile test is negative or when a complication of EBV is suspected. These tests can more precisely define the acuity of the infection (Tables 1 and 2). Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies directed against the Epstein Barr viral capsid antigen (VCA) are usually present early on in the clinical illness. VCA-IgM levels wane approximately 3 months later; thus, they are a reliable marker of acute infection. VCA-IgG antibodies persist for life and are a marker of prior EBV infection.

Table1. Serologic studies and the timing of infections

Table 2. Epstein-Barr virus antibodies and the timing of infections

IgG antibodies to EBV nuclear antigen (EBNA) appear 6 to 12 weeks after the onset of symptoms and persist throughout life. Their presence early in the course of an illness therefore excludes acute EBV infection. IgG antibodies to EBV early antigen (EA) are present at the onset of clinical illness. The presence of EA antibodies is consistent with recent infection, since titers disappear after recovery, but their absence does not exclude acute illness, because the antibodies are not expressed in a significant number of patients.

The interpretation of EBV antibody tests is based on these assumptions:

 1. After the person becomes infected with EBV, the anti-VCA IgG antibodies appear first.

2. Anti-EA (EA-D or EA-R) antibodies appear next or are present with anti-VCA antibodies early in the course of illness. An anti-EA antibody titer greater than 80 in a patient 2 years after acute infectious mononucleosis indicates chronic EBV syndrome.

3. As the patient recovers, anti-VCA IgG and anti-EA antibodies decrease, and anti-EBNA antibodies appear. Anti-EBNA antibodies persist for life and reflect a past infection.

4. After the patient is well, anti-VCA IgG and anti-EBNA antibodies are always present but at lower ranges. Occasionally, anti-EA antibodies also may be present after the patient recovers.

Procedure and patient care

• See inside front cover for Routine Blood Testing.

 • Fasting: no

• Blood tube commonly used: verify with laboratory

• Obtain serum samples as soon as possible after the onset of the illness.

• Obtain a second blood specimen 14 to 21 days later.

Abnormal findings

 - Infectious mononucleosis

- Chronic fatigue syndrome

- Chronic EBV carrier state

 - Burkitt lymphoma

- Nasopharyngeal cancer

- Posttransplant lymphoproliferative disease