Does the Epstein-Barr Nuclear Antigen (EBNA) test diagnose Epstein-Barr Virus (EBV) induced infectious mononucleosis?

From the Guidelines

The EBNA (Epstein-Barr Virus Nuclear Antigen) test is used to detect antibodies against EBV, but it is not the primary test for diagnosing acute mononucleosis, as EBNA antibodies typically appear 6-12 weeks after initial infection and remain detectable for life 1. This test is particularly useful for determining the stage of EBV infection. For acute infection diagnosis, doctors usually order tests for other EBV antibodies such as VCA-IgM (Viral Capsid Antigen IgM) which appears earlier in the infection. The EBNA test is more valuable for determining if someone has had a past EBV infection rather than diagnosing a current case of mononucleosis. When interpreting EBV serology, the pattern of different antibodies (VCA-IgM, VCA-IgG, and EBNA) helps clinicians determine whether the infection is acute, recent but resolving, or occurred in the distant past 1. Some key points to consider when using the EBNA test include:

• The presence of VCA IgM (with or without VCA IgG) antibodies in the absence of antibodies to EBNA indicates recent primary infection with EBV 1.
• The presence of EBNA antibodies indicates infection more than 6 weeks from the time of the sample and therefore not likely implicating EBV as a cause 1.
• Over 90% of the normal adult population has IgG class antibodies to VCA and EBNA antigens, although approximately 5%–10% of patients who have been infected with EBV fail to develop antibodies to the EBNA antigen 1. It's also important to note that the Monospot test, which is often used to diagnose EBV infection, can be falsely negative in up to 10% of cases, especially in younger children 1. In such cases, EBV-specific serologic testing can be used to achieve a definitive diagnosis 1.

From the Research

EBNA EBV Nuclear Antigen Test for Mononucleosis

• The EBNA EBV Nuclear Antigen test is used to diagnose Epstein-Barr virus (EBV) infections, including mononucleosis 2, 3, 4, 5, 6.
• The test detects the presence of antibodies to the EBV nuclear antigen (EBNA) in a patient's blood sample 3, 5.
• The presence of EBNA antibodies indicates a past infection, while the absence of these antibodies suggests a current or recent infection 3.
• The test is often used in combination with other tests, such as those for viral capsid antigen (VCA) IgG and IgM, to determine the stage of EBV infection 2, 4, 6.
• Studies have shown that the EBNA EBV Nuclear Antigen test has high sensitivity and specificity for detecting EBV antibodies 5, 6.
• However, the test may not always be able to distinguish between a current and past infection, and additional tests may be needed to confirm the diagnosis 3.

Performance of EBNA EBV Nuclear Antigen Tests

• The performance of EBNA EBV Nuclear Antigen tests can vary depending on the specific test used and the laboratory performing the test 2, 4, 6.
• Some studies have reported high sensitivity and specificity for certain EBNA EBV Nuclear Antigen tests, such as the Architect EBV VCA IgG, VCA IgM, and EBNA-1 IgG chemiluminescent microparticle assays 6.
• Other studies have reported lower sensitivity and specificity for certain tests, such as the DiaSorin ELISA 4.
• The choice of test and laboratory may affect the accuracy of the results, and healthcare providers should consider these factors when interpreting test results 2, 4, 6.

Clinical Applications of EBNA EBV Nuclear Antigen Tests

• The EBNA EBV Nuclear Antigen test is commonly used to diagnose mononucleosis and other EBV-related illnesses 2, 3, 4, 5, 6.
• The test can also be used to determine the stage of EBV infection and to monitor the effectiveness of treatment 3.
• In addition, the test may be used to screen for EBV infection in certain populations, such as blood donors or organ transplant recipients 5.
• Healthcare providers should consider the clinical context and the results of other diagnostic tests when interpreting the results of the EBNA EBV Nuclear Antigen test 2, 3, 4, 5, 6.