What does a positive Epstein-Barr Virus (EBV) antigen Immunoglobulin G (IgG) result mean?

Interpretation of Positive EBV Antigen IgG Results

A positive Epstein-Barr Virus (EBV) antigen IgG result most commonly indicates past infection with EBV, meaning the person has been previously infected and now has immunity. 1

Serological Patterns and Their Interpretation

EBV serological testing involves multiple markers that help determine the stage of infection:

• Past infection (most common interpretation of positive IgG):

  • VCA IgM negative
  • VCA IgG positive
  • EBNA IgG positive
  • This pattern indicates infection that occurred more than 6 weeks ago 1

• Acute primary infection:

  • VCA IgM positive
  • VCA IgG positive
  • EBNA IgG negative
  • This pattern indicates infection within the previous 6 weeks 1

• No previous infection:

  • VCA IgM negative
  • VCA IgG negative
  • EBNA IgG negative 1

Clinical Significance of Positive EBV IgG

• Lifelong immunity: Once infected with EBV, individuals develop IgG antibodies that persist for life
• No active infection: In immunocompetent individuals, a positive EBV IgG alone without other positive markers generally does not indicate active disease
• Potential for reactivation: In certain circumstances, particularly in immunocompromised patients, EBV can reactivate despite the presence of IgG antibodies 1

Important Considerations in Interpretation

Avidity Testing

• IgG avidity testing can help distinguish between recent and past infection:
  • Low avidity indicates recent infection
  • High avidity suggests past infection or reactivation 1, 2
• This is particularly useful in cases with ambiguous serological patterns 1

Potential Pitfalls in Interpretation

1. Simultaneous presence of multiple markers: VCA IgG, VCA IgM, and EBNA-1 antibodies can occur together in both late primary infection and during subclinical viral reactivation 3

2. False positives: IgM antibodies may persist or reactivate in some individuals, leading to confusing serological pictures 4

3. Heterophile antibodies: The presence of heterophile antibodies alongside positive IgG can help differentiate primary infection (94% have heterophile antibodies) from reactivation (only 5% have heterophile antibodies) 3

When Additional Testing Is Warranted

• Quantitative EBV viral load by PCR should be considered when:

  • Symptoms are persistent or severe
  • There is concern for active viral replication 1
  • Serological results are ambiguous 5

• Special populations requiring monitoring:

  • Immunocompromised patients
  • Patients on immunosuppressive therapy
  • Post-hematopoietic stem cell transplant patients 1

Practical Implications

• Screening before immunomodulator therapy: The American Gastroenterological Association and European Crohn's and Colitis Organisation recommend EBV IgG screening before starting immunomodulator therapy 1

• Monitoring for complications: Patients with chronic active EBV infection should be monitored for complications such as:

  • EBV-related hemophagocytic lymphohistiocytosis
  • T-cell or NK-cell lymphoproliferative disorders/lymphomas
  • Hematological abnormalities 1