What antibodies does the Human Herpesvirus 6 (HHV-6) test detect?

Human Herpesvirus 6 (HHV-6) Antibody Testing

The HHV-6 antibody test detects antibodies that cannot distinguish between the two variants of HHV-6 (HHV-6A and HHV-6B) and is not recommended as the primary diagnostic method for active HHV-6 infection. 1, 2

Antibody Testing Characteristics

• HHV-6 antibody tests detect:

  • IgG antibodies - indicate past or current infection
  • IgM antibodies - theoretically indicate recent infection, but have limitations

• Key limitations of antibody testing:

  • Cannot differentiate between HHV-6A and HHV-6B variants 2, 1
  • IgM detection is a poor indicator of recent infection (approximately one-third of patients with recurrent genital herpes caused by HSV-2 have IgM responses) 2
  • May reflect cross-reactivity with other herpesviruses, particularly CMV 1
  • Not reliable in immunocompromised patients 1

Diagnostic Value and Recommendations

• Antibody testing is not indicated in hematopoietic stem cell transplant (HSCT) patients 2
• Elevated HHV-6 antibody titers alone have limited clinical significance 1
• Four-fold or greater increase in anti-HHV-6 antibody titers between acute and convalescent serum samples may indicate active infection 1
• IgM anti-HHV-6 detection in infants and young children may indicate active infection 1

Preferred Diagnostic Methods

• Quantitative PCR is the mainstay of HHV-6 diagnosis and should:

  • Distinguish between HHV-6A and HHV-6B 2, 1
  • Be performed on appropriate specimens (plasma, serum, whole blood, or CSF) 1
  • Use consistent DNA extraction methods and specimen types for repeat testing 2

• Detection in cell-free plasma suggests active viral replication with the following threshold values:

  • Whole Blood: >5.5 log10 copies/mL
  • Serum: 100-fold lower than whole blood 1

Special Considerations

• In cases of suspected chromosomally integrated HHV-6 (CIHHV-6):

  • High levels of HHV-6 DNA will be consistently detected in blood 2
  • Antibody tests are not helpful in distinguishing CIHHV-6 from active infection 2
  • PCR testing of blood and non-hematopoietic tissues may be necessary 2

• For encephalitis diagnosis:

  • CSF PCR is recommended, but should be complemented by serology in some cases 2
  • A positive HHV-6 CSF PCR should prompt corresponding evaluation of blood PCR levels to distinguish between chromosomal integration and acute infection 2

Clinical Pitfalls to Avoid

• Do not rely solely on antibody testing for diagnosis of active HHV-6 infection
• Do not use IgM detection alone to confirm recent infection
• Do not assume that positive HHV-6 antibody results indicate the cause of current symptoms
• Remember that antibody avidity testing may help distinguish between primary and recurrent infection in some cases 3