What does the presence of Epstein-Barr virus (EBV) nuclear antigen Immunoglobulin G (IgG) indicate?

EBV Nuclear Antigen IgG Interpretation

The presence of EBNA IgG indicates past EBV infection that occurred more than 6-8 weeks ago, essentially ruling out EBV as the cause of current acute symptoms. 1

What EBNA IgG Tells You

• EBNA antibodies develop 1-2 months after primary EBV infection and persist for life, making them a reliable marker of remote infection 1
• The presence of EBNA IgG indicates infection occurring more than 6 weeks prior to testing, according to the Infectious Diseases Society of America 1
• In the context of diagnostic testing, EBNA IgG positivity effectively excludes acute EBV infection as the cause of current symptoms 1

Diagnostic Patterns Using EBNA IgG

The interpretation of EBNA IgG depends critically on the accompanying antibody profile:

Acute Primary Infection Pattern

• VCA IgM positive + VCA IgG positive + EBNA IgG negative = recent primary EBV infection 1, 2
• The absence of EBNA antibodies in the presence of VCA antibodies is the hallmark of acute infection 1

Past Infection Pattern

• VCA IgG positive + EBNA IgG positive + VCA IgM negative = past infection, not acute 3
• This is the most common pattern seen in the general population, as most adults have had prior EBV exposure 1

Equivocal Patterns Requiring Additional Testing

• If VCA IgG is present alone without VCA IgM or EBNA IgG, the timing is unclear and requires IgG avidity testing 3
• When all three markers (VCA IgM, VCA IgG, and EBNA IgG) are simultaneously positive, this may represent recent infection or reactivation and warrants avidity testing 3

Important Caveats

• 5-10% of truly infected patients may lack EBNA antibodies, which is a recognized limitation of serologic testing 1
• In immunocompromised patients (transplant recipients, HIV-infected individuals), quantitative EBV viral load testing by NAAT is more reliable than serology alone 1, 4
• False positive IgM results are common in patients with activated immune systems, particularly those with systemic lupus erythematosus, making EBNA IgG status even more valuable for confirming past infection 4

Clinical Application Algorithm

When you see EBNA IgG positive:

1. Check VCA IgM status: If negative, this confirms past infection and excludes acute EBV 1
2. If VCA IgM is also positive: Consider IgG avidity testing, as this may represent recent infection (low avidity) versus false positive IgM with reactivation (high avidity) 5, 3
3. In immunocompromised patients: Do not rely on serology alone; obtain quantitative EBV DNA viral load testing 1

When EBNA IgG Appears Isolated

• A profile showing only EBNA IgG positive (without VCA antibodies) should prompt confirmatory testing with immunoblotting or repeat testing, as this is an unusual pattern 3