What is the difference between Epstein-Barr Virus (EBV) Immunoglobulin G (IgG) and Immunoglobulin M (IgM)?

Difference Between EBV IgG and IgM

EBV IgM indicates acute primary infection (within 6 weeks), while EBV IgG indicates past infection (>6 weeks) when accompanied by EBNA IgG positivity. 1

Serological Patterns and Interpretation

EBV antibody testing is crucial for determining the stage of Epstein-Barr virus infection. The standard panel includes three key markers:

1. Viral Capsid Antigen (VCA) IgM:

   • Appears early in infection
   • Peaks during acute phase
   • Typically disappears within 8-10 weeks 2
   • Positive result suggests recent/acute infection

2. Viral Capsid Antigen (VCA) IgG:

   • Develops rapidly during acute infection
   • Remains at relatively constant levels for life
   • Indicates exposure to EBV (current or past)

3. Epstein-Barr Nuclear Antigen (EBNA) IgG:

   • Appears weeks to months after initial infection
   • Persists for life
   • Absence during acute infection, presence indicates past infection

Diagnostic Interpretation

The following patterns help distinguish between infection stages 1:

• 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:

  • VCA IgM (-), VCA IgG (-), EBNA IgG (-)

Diagnostic Challenges

Several situations may complicate interpretation:

• Simultaneous presence of all three markers (VCA IgM, VCA IgG, and EBNA IgG) can indicate either:

  • Late primary infection (transitional phase)
  • Reactivation of latent infection 3

• IgG avidity testing helps distinguish between:

  • Low avidity: recent primary infection
  • High avidity: past infection or reactivation 1, 3

• Heterophile antibody testing provides additional diagnostic value:

  • Present in 94% of primary infections
  • Rarely present (5%) in reactivation cases 3

Clinical Applications

1. Screening before immunomodulator therapy:

   • EBV IgG screening should be considered before starting immunomodulator therapy 4
   • Anti-TNF monotherapy might be preferred over thiopurines in EBV seronegative patients

2. Diagnostic approach:

   • Single antibody tests at symptom onset may lead to misdiagnosis
   • Optimal testing includes acute and convalescent samples (10-14 days apart) 1
   • The Paul-Bunnell and monospot tests are suboptimal for diagnosis 4

3. Monitoring in immunocompromised patients:

   • Immunocompromised patients are at increased risk for lymphoproliferative disorders
   • Viral load monitoring may be indicated in high-risk patients 1

Common Pitfalls

• Relying on a single antibody test at symptom onset
• Waiting too long (>4 weeks) for convalescent sample may miss the diagnostic window for VCA IgM
• Not accounting for atypical antibody responses in immunocompromised patients
• Failing to consider heterophile antibody testing as a complementary diagnostic tool 1

Remember that serological methods are preferred over PCR for routine diagnosis of past EBV infection, as PCR primarily indicates active viral replication 1.