Antibody Tests For The Epstein-Barr Virus (EBV)

Typically, the Epstein-Barr virus (EBV) causes mild to moderate illnesses. Epstein-Barr virus blood tests detect antibodies for EBV within the blood and help to establish an EBV infection diagnosis.

The Epstein-Barr virus is a very common infection. The Centers for Disease Control and Prevention (CDC) reports that most individuals in the United States at some point within their lives are infected with EBV. It is a very contagious virus and passes from one person to the next easily. Infected individuals have the virus in their saliva, and it may be spread via close contact like sharing cups or utensils or through kissing.

After being initially exposed to Epstein-Barr Virus, there is a several week time period before the associated symptoms start to appear, which is referred to as the incubation period. Throughout the acute primary infection phase, the virus continues to multiply. That is followed by a reduction in viral numbers and symptoms being resolved. However, the virus never disappears completely. Latent EBV stays inside people’s bodies for the rest of their lives and might reactivate but normally does not cause too many problems unless a person has a significantly weakened immune system. 

Most individuals are infected by Epstein-Barr Virus when they are children and experience no or few symptoms. However, whenever the initial infection takes place in adolescence, it might cause infectious mononucleosis, which is commonly referred to as mon. This condition is associated with an enlarged spleen, swollen lymph nodes, sore throat, fever, fatigue, and an enlarged liver at times. Those symptoms arise in around 25% of infected young adults and teenagers and normally are resolved within a few months. 

People who have mono are usually diagnosed based on their symptoms and the results from a mono test (that tests for a heterophile antibody) and complete blood count (CBC). Around 25% of individuals with mononucleosis do not produce any heterophile antibodies and end up with a negative mono test. That is particularly true for children. EBV antibody tests may be used to determine whether a current EBV virus infection is causing the symptoms that individuals are experiencing.

The most common cause of mononucleosis is EBV. The CDC reports that examples of other mono causes include toxoplasmosis, rubella, hepatitis C, hepatitis B, hepatitis A, and cytomegalovirus (CMV). 

It can sometimes be important to be able to distinguish EBV from those other illnesses. For example, in pregnant women, it might be important to diagnose the causes of viral illness symptoms. Testing may help with distinguishing a primary EBV infection, which hasn’t been shown that it affects a developing infant, from toxoplasmosis infection, herpes simplex virus, or CMV, since those illnesses might cause complications while a woman is pregnant and harm the fetus.

It might also be important to rule an Epstein-Barr Virus infection out and search for other issues that are causing the symptoms. For example, for a person with strep throat, which is an infection that group A streptococcus causes, needs to be identified and then treated using antibiotics. An individual might have strep throat rather than mononucleosis or might have both conditions simultaneously.

Several tests are available for different classes and types of Epstein-Barr Virus antibodies. These antibodies are proteins that are produced by the human body as an immune response to several Epstein-Barr virus antigens. Throughout a primary EBV infection, the levels of the EBV antibodies rise and fall at different times as the infection continues to progress. Measuring the antibodies within the blood can help with diagnosis and usually provide the healthcare professional with information on the stage of the infection and whether the infection is past, recent, or current. 

  • Antibody – Timing of when an antibody is usually detected within the blood
  • Viral Capsid Antigen (VCA)-IgM Antibody – First appears after being exposed to the virus and then after around 4 to 6 weeks tends to disappear.
  • VCA-IgG antibody – Arises during acute infection. The level is highest at 2-4 weeks, and then sees a slight drop, stabilizes, and then remains present in the person’s body for the rest of their life.   
  • Early Antigen (EA-D) antibody – Arises during an acute infection phase. It then tends to go away. Around 20% of people who are infected will continue having quantities that are detectable for several years once the EBV infection is resolved.
  • Epstein-Barr Nuclear Antigen (EBNA) antibody – Normally does not arise until after the acute infection is resolved. It starts to develop around 2-4 months following the initial infection and is present for life after that.

How are the tests used?

Epstein-Barr virus (EBV) antibody blood tests are used to assist with diagnosing EBV infection, which is the most common cause of mono (infectious mononucleosis) if an individual is symptomatic, but their mono test is negative.

In pregnant women who have viral illness symptoms one or several EBV antibody tests might be ordered in addition to tests for toxoplasmosis, cytomegalovirus (CMV), and other infections (that are sometimes part of the TORCH screen) to assist with distinguishing between EBV and other conditions that might result in similar symptoms.

Those tests might be ordered if an asymptomatic individual has been exposed to EBV previously or is susceptible to developing a primary EBV infection. It is not performed routinely but might be ordered when a person, such as an immunocompromised individual or an adolescent, has come into close contact with someone who has mononucleosis. 

It is recommended by the Centers for Disease Control and Prevention (CDC) that several tests be ordered to help determine whether an individual is susceptive to EBV or for detecting a reactivated EBV infection, prior infection, or recent infection.

Those tests include the following:

When are the tests ordered?

EBV antibody tests can be ordered whenever a person has symptoms that suggest mono but where the mono test comes back negative and whenever a pregnant woman exhibits flu-like symptoms. The healthcare provider would like to determine whether her symptoms are being caused by EBV or another type of microbe.

Some symptoms and signs that are associated with mononucleosis include the following:

  • Swollen lymph glands in the armpits and/or neck
  • Sore throat
  • Headache
  • Fever
  • Extreme fatigue or weakness
  • Enlarged liver and/or spleen (sometimes)

Testing might be ordered whenever a healthcare professional is looking to establish prior exposure to EBV. Also, testing might be repeated occasionally whenever the healthcare provider wants to track concentrations (titers) of antibodies and/or whenever the initial test is negative, but the healthcare provider still suspects that EBV is causing the individual’s symptoms.

What do the test results mean?

Care needs to be taken whenever EBV antibody testing results are interpreted. The symptoms and signs, in addition to the medical history of the individual who is being tested, need to be factored in. A healthcare practitioner might consult with an infectious disease specialist, specifically one who has experience with EBV testing.  

If a person tests positive for VCA-IgM antibodies, most likely, the individual does have an EBV infection, and it might be early in the overall course of the illness. If the person has symptoms that are associated with mono as well, then most likely, the individual will be diagnosed with having mononucleosis, even if their mono test results were negative.

  • If a person has positive EA-D IgG and VCA-IgG tests, then it is very likely that the individual has a recent or current EBV infection.
  • If the EBNA and VCA-IgG are positive, but the VCA-IgM is negative, then most likely, the individual who has been tested had an EBV infection in the past.
  • If a person is asymptomatic and tests negative for VCA-IgG, then most likely, the person has not been exposed to EBV previously and is vulnerable to the infection.

Increasing VCA-IgG levels tend to indicate that the person has an active EBV infection. On the other hand, decreasing concentrations tend to indicate an EBV infection that is recent and resolving. However, a practitioner needs to be careful when they are interpreting concentrations of EBV antibodies since the amount of antibody that is present doesn’t correlate with how severe the infection is or how long it is going to last. High VCA-IgG levels might be present and continue to persist at this concentration for the rest of the individual’s life.

Is there anything else that is important for me to know?

A ruptured spleen is the most type of mono complication. Other EBV infection complications that may occur include having difficulty breathing due to having a swollen throat, and, rarely, encephalitis, seizures, pancreatitis, skin rashes, and/or jaundice. EBV also is associated with and might play a role in several rare types of cancer, including nasopharyngeal carcinoma, Hodgkin lymphoma, and Burkitt’s lymphoma, in addition to fibromyalgia and multiple sclerosis.

Rarely is the reactivation of the virus a health concern unless the individual is persistently and significantly immunocompromised, as can happen in organ transplant recipients or those with HIV/AIDS. Primary infections in those individuals might be more serious, and some might suffer chronic EBV-related symptoms.