Biomarkers for Epstein Barr Virus Infection

Optimal Takeaways

Measuring Epstein Barr virus (EBV) antibodies provides a snapshot of whether and when someone has been exposed to EBV.

An estimated 90% of adults have been infected with the Epstein Barr virus, also known as Human Herpesvirus 4. Though EBV is best known as the most common cause of infectious mononucleosis, it can also cause meningitis, encephalitis, myelitis, facial nerve palsies, hemiplegia, sleep disorders, psychoses, acute cerebellar ataxia, Guillain-Barre syndrome, compromised immunity, neutropenia, acquired hypogammaglobulinemia, pneumonia, interstitial lung disease, pancreatitis, and myocarditis (CDC 2020).

Past infection with EBV has been associated with lymphoma, nasopharyngeal and stomach cancer, autoimmune disorders such as lupus, multiple sclerosis, rheumatoid arthritis, Sjogren’s syndrome, and autoimmune hepatitis, and possibly autoimmune thyroid disorders (Dittfeld 2016).

A prospective study of 901 patients with early-stage multiple sclerosis (MS) found EBV antibodies in 100% of the cohort. This supports prior research suspecting that EBV may play a role in the onset of MS (Abrahamyan 2020). Cut-offs in the study were as follows: VCA IgG below 20 U/mL was considered negative, and 20 U/mL or above was considered positive; VCA IgM below 20 U/mL was negative, 20-40 U/mL was equivocal, and 40 U/mL or above was positive; EBNA IgG below 5 U/mL was considered negative, 5-20 U/mL was considered equivocal, and 20 U/mL or above was positive.

EBV Ab VCA, IgG

The EBV Ab VCA, IgG antibody peaks 2-4 weeks after exposure/onset, so very high levels suggest an acute infection. The IgG antibody to EBV viral capsid antigen (VCA) is an immunoglobulin that is measurable in the acute phase of infection. It peaks 2-4 weeks following onset, after which it declines. It is expected to persist at some level throughout an individual’s lifetime (CDC 2020).

Low VCA IgG antibody levels suggest the absence of an acute EBV infection though it does not rule out past infection. Some individuals may have an active infection but still not have detectable VCA IgG antibodies though this is rare (CDC 2020).

High VCA IgG antibody levels indicate the presence of an acute infection.

EBV Ab VCA, IgM

Low VCA IgM antibody indicates that an active infection is not present but does not rule out past infection.

High VCA IgM indicates a new or recent infection.

The IgM antibody to EBV VCA appears early in the infection but usually will disappear within 4-6 weeks. If EBV VCA IgM antibodies are present, but EB nuclear antigen (EBNA) antibodies are absent, it is considered a new or recent infection (CDC 2020).

A level of VCA IgM below 20 U/mL was negative in a prospective cohort study of multiple sclerosis, whereas a level of 20-40 U/mL was equivocal, and 40 U/mL or above was positive (Abrahamyan 2020).

EBV Nuclear Antigen (EBNA) Ab, IgG

Low EBNA IG antibody levels indicate the absence of past EBV infection but do not rule out current new infection.

High EBNA IgG antibody indicates past infection with EBV.

The presence of EBV nuclear antigen (EBNA) antibody indicates past EBV infection. The EBNA antibody does not appear until 2-4 months following infection but then persists throughout an individual’s life (CDC 2020).

In one study of multiple sclerosis patients, EBNA IgG below 5 U/mL was considered negative, 5-20 U/mL was considered equivocal, and 20 U/mL or above was positive (Abrahamyan 2020).  

EBV Early Antigen Ab, IgG

Low levels of early antigen IgG indicate that an acute EBV infection is not present.

High levels of early antigen IgG indicate an acute phase of infection. Elevated antibodies may persist in some individuals even after the acute phase has passed.

Early antigen IgG antibodies are present during the acute phase of EBV infection. They usually decline and become undetectable 3-6 months following infection though levels may be maintained in approximately 20% of individuals (CDC 2020).

Ranges

References

Abrahamyan, Sargis et al. “Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis.” Journal of neurology, neurosurgery, and psychiatry vol. 91,7 (2020): 681-686. doi:10.1136/jnnp-2020-322941

Centers for Disease Control and Prevention. Laboratory Testing Epstein Barr Virus (EBV). Reviewed September 28, 2020. Healthcare Providers.

Dittfeld, Anna et al. “A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders.” Central-European journal of immunology vol. 41,3 (2016): 297-301. doi:10.5114/ceji.2016.63130