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

Interpretation of Positive EBV Capsid Antibody IgG Results

A positive Epstein-Barr Virus (EBV) capsid antibody IgG (VCA IgG) result indicates past infection with EBV, especially when accompanied by positive EBNA IgG and negative VCA IgM. 1

Serological Patterns and Their Interpretation

EBV infection diagnosis relies on specific serological patterns that help distinguish between acute and past infections:

• Pattern interpretation according to American Journal of Hematology guidelines:
  • VCA IgM (+), VCA IgG (+), EBNA IgG (-): Acute primary infection (within 6 weeks)
  • VCA IgM (-), VCA IgG (+), EBNA IgG (+): Past infection (>6 weeks)
  • VCA IgM (-), VCA IgG (-), EBNA IgG (-): No previous EBV infection 1

This standardized interpretation is crucial as EBV serology can yield up to 32 possible serological patterns, though research shows only 12 patterns occur with significant frequency 2.

Clinical Significance of Positive VCA IgG

A positive VCA IgG result has different implications depending on other antibody results:

1. When VCA IgG is positive with positive EBNA IgG and negative VCA IgM:

   • Indicates past EBV infection (>6 weeks ago)
   • Patient has developed immunity to EBV
   • No active infection requiring treatment 1

2. When VCA IgG is positive with positive VCA IgM and negative EBNA IgG:

   • Suggests acute primary infection (within 6 weeks)
   • May correlate with clinical symptoms of infectious mononucleosis 1

3. When VCA IgG, VCA IgM, and EBNA IgG are all positive:

   • This pattern can be challenging to interpret
   • May represent either late primary infection or reactivation
   • IgG avidity testing is recommended to differentiate between these scenarios 1, 3

Using Avidity Testing for Clarification

When serological patterns are ambiguous, IgG avidity testing provides valuable additional information:

• Low avidity VCA IgG indicates recent primary infection
• High avidity VCA IgG suggests past infection or reactivation
• In one study, among patients with VCA IgG, VCA IgM, and EBNA-1 antibodies present, 42% had late primary infection while 49% had high-avidity IgG antibodies indicating reactivation 3, 4

Monitoring and Management Implications

For patients with evidence of past EBV infection (positive VCA IgG):

• No specific treatment is typically required for past infections
• For immunocompromised patients, monitoring may be warranted:
  • The American Gastroenterological Association and European Crohn's and Colitis Organisation recommend EBV IgG screening before starting immunomodulator therapy
  • Patients on immunosuppressive therapy with evidence of EBV infection are at increased risk for complications and lymphoproliferative disorders 1

Common Pitfalls in Interpretation

1. Misinterpreting isolated positive VCA IgG:

   • A common error is assuming active infection based solely on positive VCA IgG
   • VCA IgG remains positive for life after infection and indicates immunity, not active disease

2. Overlooking the need for comprehensive serology:

   • Interpretation requires assessment of multiple markers (VCA IgM, VCA IgG, EBNA IgG)
   • Isolated testing of single antibodies can lead to incorrect conclusions

3. Confusing reactivation with primary infection:

   • The presence of heterophile antibodies can help differentiate:
     • Present in 94% of primary infections
     • Present in only 5% of reactivation cases 3

4. Relying solely on EA antibodies for reactivation diagnosis:

   • Research shows EBV PCR is positive in only 3% of sera with elevated antibodies against EA, questioning the utility of EA titers for diagnosing EBV reactivation 5

In summary, a positive EBV VCA IgG result most commonly indicates past infection and immunity when accompanied by positive EBNA IgG. The complete antibody profile, including VCA IgM and EBNA IgG, is essential for accurate interpretation and clinical decision-making.