EBV Serology Interpretation: Normal IgM with Positive IgG
A normal (negative) EBV IgM with positive IgG indicates past EBV infection, not acute infection. 1
Serologic Pattern Interpretation
The combination of negative VCA IgM and positive VCA IgG represents resolved, past EBV infection in the vast majority of cases. 1 This pattern indicates that the acute phase of infection has passed and the patient has developed long-term immunity.
Key Diagnostic Markers
To fully interpret this serologic pattern, you need to consider the complete antibody panel:
VCA IgM negative + VCA IgG positive + EBNA positive = Past infection (most common scenario). The presence of EBNA antibodies specifically indicates infection occurring more than 6 weeks prior to testing, making EBV unlikely as the cause of current symptoms. 1
VCA IgM negative + VCA IgG positive + EBNA negative = This pattern can indicate recent primary infection (within the past 1-2 months), as EBNA antibodies develop 1-2 months after primary infection. 1 However, 5-10% of infected patients may never develop detectable EBNA antibodies, which should be considered when interpreting results. 1
When Acute Infection is Present
Recent primary EBV infection is indicated by positive VCA IgM and negative EBNA antibodies. 1 The presence of VCA IgM (with or without VCA IgG) in the absence of EBNA antibodies indicates recent primary infection. 1
Additional Confirmatory Testing
If clinical suspicion for acute infection remains high despite negative IgM:
IgG avidity testing can clarify timing of infection. Low avidity IgG indicates acute infection (within 10 days), while high avidity indicates past infection. 2, 3 More than 90% of sera show low avidity (index <0.25) during the first 10 days after symptom onset, while past infections uniformly show avidity indices of 0.5 or 1.0. 3
Recent primary infection was documented in only 1.8% of immunocompetent patients with negative VCA-IgM when avidity testing was performed. 2
Important Clinical Pitfalls
False positive IgM can occur in patients with activated immune systems, including those with systemic lupus erythematosus (SLE), making IgM results potentially misleading. 4
Reactivation patterns can show positive IgM in the presence of high avidity IgG and positive EBNA, representing immune system activation rather than acute infection. 5 This "serological EBV reactivation" pattern does not represent a clinical entity but reflects non-specific immune activation. 5
In immunocompromised patients (transplant recipients, HIV-infected individuals), quantitative EBV viral load testing by nucleic acid amplification test (NAAT) is more reliable than serology alone. 1
Clinical Algorithm
For patients with negative IgM and positive IgG:
- Check EBNA status: If positive, this confirms past infection (>6 weeks ago). 1
- If EBNA negative: Consider IgG avidity testing to distinguish recent infection (low avidity) from past infection with absent EBNA response (high avidity). 2, 3
- If immunocompromised: Order quantitative EBV DNA viral load rather than relying on serology. 1