From the Guidelines
It is normal for Viral Capsid Antigen (VCA) IgG and Epstein-Barr Nuclear Antigen (EBNA) IgG to remain elevated or fluctuate years after primary Epstein-Barr Virus infection. After initial EBV infection, VCA IgG typically appears within 4-7 days, peaks during the acute phase, and then persists for life, as noted in the 2013 IDSA and ASM recommendations 1. EBNA IgG develops more slowly, usually appearing 3-6 weeks after infection and also remaining detectable indefinitely. These persistent antibody levels represent the immune system's long-term memory of the infection rather than indicating active disease. Some key points to consider 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, whereas the presence of EBNA antibodies indicates infection more than 6 weeks from the time of the sample 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. Minor fluctuations in antibody titers can occur due to various factors including immune system status, concurrent infections, or even laboratory testing variability. The persistence of these antibodies is a normal immunological response to EBV, which establishes lifelong latency in memory B cells after primary infection, as supported by the guidelines from the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM) 1.
From the Research
EBV Reactivation and Antibody Levels
- The levels of Viral Capsid Antigen (VCA) Immunoglobulin G (IgG) and Epstein-Barr Nuclear Antigen (EBNA) IgG can provide insight into Epstein-Barr Virus (EBV) infection status 2, 3, 4, 5, 6.
- In general, VCA IgG and EBNA IgG antibodies are indicative of past EBV infection, while the presence of VCA IgM antibodies may suggest recent or reactivated infection 2, 5.
Changes in Antibody Levels Over Time
- Studies have shown that EBV antibody levels can remain stable over time, but may also fluctuate due to various factors such as reactivation or immune system changes 3, 4.
- One study found that EBV VCA IgG and EBNA-1 IgG levels were generally stable in people with multiple sclerosis, with no significant increases in IgG titers over 12 months 3.
- Another study found that anti-EBV-VCA and EA IgG concentrations were significantly higher in patients with anti-nuclear autoantibodies (ANA) compared to healthy controls, suggesting a possible link between EBV reactivation and autoimmune diseases 4.
Interpretation of EBV Serological Patterns
- The interpretation of EBV serological patterns can be complex, with 32 possible patterns resulting from the combination of five markers (VCA IgG, VCA IgM, heterophile antibodies, EA-D, and EBNA-1) 5.
- A study developed evidence-based tools for interpreting EBV results, including two easy-to-use tables that can interpret over 95% of BioPlex serological results 5.
- Another study evaluated the Architect EBV VCA IgM, VCA IgG, and EBNA-1 IgG chemiluminescent immunoassays for assessing EBV serostatus prior to transplantation, finding good sensitivities and specificities for EBV serostatus determination 6.
EBV Reactivation and Disease Activity
- Some studies have investigated the relationship between EBV reactivation and disease activity in various conditions, such as multiple sclerosis 3 and autoimmune diseases 4.
- The results suggest that EBV reactivation may be associated with increased disease activity in some cases, but more research is needed to fully understand this relationship 3, 4.