EBV EBNA IgG Interpretation
The presence of EBNA IgG antibodies indicates past EBV infection that occurred more than 6 weeks ago, making EBV unlikely as the cause of current acute symptoms. 1
What EBNA IgG Tells You
EBNA (Epstein-Barr Nuclear Antigen) IgG antibodies develop 1-2 months after primary EBV infection and persist for life. 1, 2 This antibody pattern is found in over 90% of normal adults who have been previously infected with EBV. 3
Key interpretation principle: When EBNA antibodies are present, the infection occurred in the past—not recently—and you should look for alternative causes of the patient's current symptoms. 1
Clinical Context Matters
In Immunocompetent Patients
- Past infection pattern: EBNA IgG positive + VCA IgG positive + VCA IgM negative = remote infection, not acute disease 2, 4
- Recent infection pattern: EBNA IgG positive + VCA IgG positive + VCA IgM positive = late primary infection (6-12 weeks after symptom onset) or possible reactivation 4
Important Caveat
Approximately 5-10% of patients who have been infected with EBV fail to develop EBNA antibodies despite true past infection. 3 This means absence of EBNA doesn't always rule out past infection, but presence of EBNA definitively confirms it.
When EBNA IgG Appears Alone
An isolated EBNA IgG positive result (without VCA antibodies) is unusual and may require additional testing with IgG avidity or immunoblotting to clarify infection status. 4 This pattern can create diagnostic uncertainty and warrants correlation with clinical presentation.
Special Populations
Immunocompromised Patients
In transplant recipients, HIV-infected individuals, or those with congenital immunodeficiencies, do not rely solely on EBNA IgG serology. 1 These patients require quantitative EBV viral load testing by nucleic acid amplification (NAAT) to assess for EBV-associated lymphoproliferative disease, as serologic patterns may be unreliable. 1, 2
Chronic Active EBV Infection (CAEBV)
Markedly elevated VCA IgG titers (≥1:640) combined with elevated early antigen (EA) IgG (≥1:160) and positive IgA antibodies to VCA may indicate CAEBV, even in the presence of EBNA antibodies. 1, 2 This represents a distinct clinical entity requiring specialized evaluation.
Common Pitfalls to Avoid
- Don't diagnose acute EBV infection when EBNA IgG is present alone or with only VCA IgG—this indicates past infection 1, 2
- Don't ignore the 5-10% of patients who never develop EBNA antibodies despite true EBV infection 3
- Don't use serology alone in immunocompromised patients—viral load testing is essential 1, 2