Mononucleosis Test: Epstein-Barr Virus (EBV) Antibodies Panel

What is a mono test and why is it important?

A mono test, also known as an Epstein-Barr virus (EBV) antibody panel, is a blood test that detects the presence of antibodies produced by the body in response to the Epstein-Barr virus. It is important because it helps diagnose mono and distinguish it from other illnesses with similar symptoms.

Understanding Mono Test: EBV Antibodies Panel

Epstein-Barr (EB) virus is a herpes group virus that is ubiquitous. You can get infectious mononucleosis from it, and it may also play a part in the growth of Burkitt lymphoma, some nasopharyngeal carcinomas, and a few rare genetic lymphoproliferative disorders. The EBV test serologic response to EB virus includes antibodies to early antigen, IgM and IgG antibodies to viral capsid antigen (VCA), and antibodies to Epstein-Barr nuclear antigen (EBNA)

Epstein-Barr (EB) virus is a herpes group virus that is ubiquitous. It leads to infectious mononucleosis and may play a role in the development of Burkitt lymphoma, some nasopharyngeal carcinomas, and a few rare genetic lymphoproliferative disorders. The EBV test measures the serologic response to the EB virus, which includes antibodies to early antigen, IgM and IgG antibodies to viral capsid antigen (VCA), antibodies to Epstein-Barr nuclear antigen (EBNA), and the presence of the virus in bodily fluids, especially saliva.

You can usually tell if someone has infectious mononucleosis by their symptoms, blood count, morphology, and an EBV test that shows they have heterophile antibody. However, up to 20% of people may be heterophile-negative at presentation, and the test may become positive after a few days. In some of these cases, a small sample of blood for Epstein-Barr virus antibodies may be useful in confirming the diagnosis of infectious mononucleosis. The results of a mono test are either positive or negative. A positive test result indicates the presence of heterophile antibodies and a high level of a type of white blood cell called a lymphocyte. This result, along with a patient’s symptoms, is used to make a diagnosis of infectious mononucleosis. Many experts recommend using laboratory tests, such as a complete blood count, to confirm a diagnosis of mono. If you get a negative monospot test result but you continue to be sick with the symptoms of infectious mononucleosis, your doctor may want to do another test along with the EBV blood test.

The use of EBV serology in chronic fatigue syndrome is the most controversial. This is a condition that mostly affects young to middle-aged women and is marked by long-lasting, debilitating fatigue and a wide range of usually mild physical complaints. Because most people have a lot of EBV antibodies, they stay around for a long time, and antibody levels do not always match up with symptoms, EBV serology cannot be used to diagnose, follow, or rule out chronic fatigue syndrome. 

Test Includes:

• Epstein-Barr Virus VCA Antibody (IgM), Epstein-Barr Virus VCA Antibody (IgG), Epstein-Barr Virus Nuclear Antigen (EBNA) Antibody (IgG)

Methodology

Immunoassay (IA)

Reference Range(s)

Epstein-Barr Virus VCA Antibody (IgM)

U/mL | Interpretation

<36.00 | Negative

36.00-43.99 | Equivocal

>43.99 | Positive

Epstein-Barr Virus VCA Antibody (IgG)

<18.00 | Negative

18.00-21.99 | Equivocal

>21.99 | Positive

Epstein-Barr Virus Nuclear Antigen (EBNA) Antibody (IgG)

Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a gamma herpes virus that occurs only in humans. Laboratory testing can help distinguish whether someone is susceptible to an EBV infection or has a recent or past infection.

Healthcare providers can perform an EBV test for antibodies to the following EBV-associated antigens:

• Viral capsid antigen (VCA)
• Anti-VCA IgM appears early in an EBV infection and usually disappears within four to six weeks.
• Anti-VCA IgG appears in the acute phase of EBV infection, peaks two to four weeks after onset, declines slightly, then persists for the rest of a person’s life.
• Early antigen (EA)
• Anti-EA IgG appears in the acute phase of illness and generally falls to undetectable levels after three to six months. In many people, the detection of antibodies to EA is a sign of active infection. However, 20% of healthy people may have had antibodies against EA for years.
• EBV nuclear antigen (EBNA)
• Antibody to EBNA, determined by the standard immunofluorescent test, is not seen in the acute phase of EBV infection but slowly appears two to four months after the onset of symptoms and persists for the rest of a person’s life. Other EBNA enzyme immunoassays may report false-positive results.

Monospot Test

The monospot test, also known as the heterophile antibody test or mononucleosis spot test, is a blood test used to diagnose mononucleosis, including rubella. It finds heterophile antibodies, which are specific antibodies made by the immune system in response to the Epstein-Barr virus (EBV), and it works by doing this. These heterophil antibodies are crucial in identifying and confirming the presence of infectious mononucleosis as well as other diseases such as rubella. In most commercially available kits, a small amount of blood is placed in the sample collection window to perform the monospot test. The monospot test is a quick and easy way to diagnose mononucleosis and rubella, but it may not be accurate in all cases. False negatives can occur if the test is done too early in the illness, while false positives can occur if the patient has recently had another viral infection. Overall, the monospot test remains an important tool in diagnosing mononucleosis and helping patients receive appropriate treatment.

• The monospot test is not recommended for general use. There are other conditions besides infectious mononucleosis that can cause the antibodies that Monospot detects. Moreover, studies have shown that the monospot produces both false positive and false negative results. For example, the heterophile antibodies detected by Monospot are often not present in children with infectious mononucleosis. At best, the monospot test may indicate that a person has a typical case of infectious mononucleosis but does not confirm the presence of an EBV infection.
• Anti-VCA IgM appears early in EBV infection and usually disappears within four to six weeks.
• Anti-VCA IgG appears in the acute phase of EBV infection, peaks two to four weeks after onset, declines slightly, then persists for the rest of a person’s life.

Mononucleosis (Mono) Test

A mononucleosis (mono) test, also known as a throat culture, is a diagnostic test that helps to identify the presence of mononucleosis in the body. Mononucleosis, also known as the "kissing disease", is a viral infection caused by the Epstein-Barr virus. The symptoms of mononucleosis can last for several weeks and may include fever, sore throat, fatigue, swollen lymph nodes, muscle weakness, and a rash. During a physical exam, your doctor may look for signs such as swollen lymph nodes and tonsils to help diagnose mononucleosis. A mono test, which involves a simple blood draw, can be performed in a doctor's office or lab. The results of the test, including the throat culture, can help doctors determine if an individual has mononucleosis and what treatment options are available. Antibiotics don't work against viral infections such as mono. Treatment mainly involves taking care of yourself, such as getting enough rest, eating a healthy diet, and drinking plenty of fluids. You may take over-the-counter pain relievers to treat a fever or sore throat.

Interpretation of EBV Tests

EBV antibody tests are not usually needed to diagnose infectious mononucleosis. But certain lab tests, like EBV antibody testing and mononucleosis testing, might be needed to find out what is wrong with people who do not have infectious mononucleosis or who have other illnesses that can be caused by EBV infection. Symptoms of infectious mononucleosis generally resolve within four weeks. If a person is ill for more than six months and does not have a laboratory-confirmed diagnosis of EBV infection, other causes of chronic illness or chronic fatigue syndrome should be considered. There are different types of EBV antibodies that can be detected through these laboratory tests. If certain types of antibodies are found, it may mean you were infected recently with mono. Other types of EBV antibodies may mean you were infected in the past. Many experts recommend EBV antibody tests, mononucleosis testing, and a complete blood count to confirm a recent mono infection.

The interpretation of EBV antibody tests requires familiarity with these tests and access to the patient’s clinical information.

The interpretation of EBV antibody tests and the diagnosis of EBV infection is summarized as follows:

• Susceptibility to infection
• People are considered susceptible to EBV infection if they do not have antibodies to the VCA.
• Primary (new or recent) infection
• People are considered to have a primary EBV infection if they have anti-VCA IgM but do not have antibodies to EBNA. A high or rising level of anti-VCA IgG and no antibody to EBNA after at least four weeks of illness are also strong signs of a primary infection. Resolution of the illness may occur before the diagnostic antibody levels appear. In rare cases, people with active EBV infections may not have detectable EBV-specific antibodies.
• Past infection
• The presence of antibodies to both VCA and EBNA suggests a past infection (from several months to years earlier). Since over 90% of adults have been infected with EBV, most adults will show antibodies to EBV from infection years earlier. High or elevated antibody levels may be present for years and are not diagnostic of recent infection.

Testing paired acute- and convalescent-phase serum samples is not useful to distinguish between recent and past EBV infections. In most cases, the antibody response occurs rapidly during the primary EBV infection. There are signs of infectious mononucleosis and the presence of IgG and IgM anti-VCA antibodies at the same time. However, the antibody pattern is not stable before symptoms appear.