Epstein-Barr virus (EBV) antibodies

What is being analysed?
Epstein-Barr virus (EBV) antibodies are a group of tests used to help diagnose a current, recent or past EBV infection. EBV belongs to the herpesvirus family. The virus is spread through saliva and causes a very common infection. According to the Centers for Disease Control and Prevention (CDC), 95% of people in the United States will be infected with EBV by the age of 40. After exposure to the virus there is an incubation period of several weeks. EBV then causes a primary, acute infection, followed by resolution and latency. EBV remains in the body for the rest of the person’s life, reactivating intermittently, usually without consequences except in people whose immune system is significantly weakened.

Most people infected with EBV in childhood have few or no symptoms, even in the acute phase of the infection. However, when the first infection happens in adolescence, EBV causes infectious mononucleosis in about 35-50% of those infected. Mononucleosis is associated with tiredness, fever, sore throat, swollen lymph nodes, an enlarged spleen and sometimes an enlarged liver. When symptoms occur, they last for a month or two before the initial infection resolves. Mononucleosis is diagnosed on the basis of the patient’s symptoms, the full blood count and the mono test (a screening test for heterophile antibodies). A certain percentage of people with mononucleosis have a negative mono test; this is particularly true in children. EBV antibodies may be measured to assess whether the patient’s symptoms are due to an acute EBV infection or not. Antibody testing is also important to distinguish EBV infection from other infections.
An enlarged spleen caused by mononucleosis can in fact rupture. Patients with mononucleosis should avoid contact sports for many weeks or months after the infection, as a ruptured spleen can be a serious complication. In pregnant women with symptoms of a viral illness, it is also necessary to distinguish a primary EBV infection, which has not been shown to be transmitted to the foetus, from infection with cytomegalovirus (CMV), herpes simplex virus or Toxoplasma, since CMV, HSV and Toxoplasma can cross the placenta and harm the foetus. It is also important to be able to rule out EBV and identify the cause of the symptoms. Streptococcal throat and tonsil infections must also be diagnosed and distinguished from EBV infection, as they need to be treated with antibiotics; the two infections can also occur together in the same patient. There are several EBV antibodies. They are proteins produced by the body as an immune response to Epstein-Barr virus antigens. They include IgM and IgG antibodies against the viral capsid antigen (VCA), IgG antibodies against the early antigen D (EA-D) and IgG antibodies against the nuclear antigen (EBNA). During a primary EBV infection, each of these antibodies appears in the blood at its own time.

VCA-IgM antibodies appear first and tend to disappear about 4-6 weeks after the start of the infection. VCA-IgG antibodies then appear, peak after 2-4 weeks, fall slightly, stabilise and remain in the blood for life. EA-D IgG appears during the acute phase of infection and then tends to disappear after 3-6 months; about 20% of patients still have measurable EA-D IgG for many years after the EBV infection has resolved. EBNA-IgG does not usually appear until the acute infection has resolved. It usually appears about 2-4 months after the initial infection and remains for life. By assessing the results of tests for the different EBV antibodies, the doctor can tell whether the infection is current, recent or past.

How is the sample collected for testing?
The blood sample is taken from a vein.

How is it used?
Epstein-Barr virus (EBV) antibodies are tested to help diagnose mononucleosis when the patient has symptoms but the mono test is negative. The Centers for Disease Control and Prevention (CDC) recommends requesting:

IgG and IgM antibodies against the viral capsid antigen (VCA) and IgG antibodies against the early antigen D (EA-D) to detect a current or recent infection, and IgG antibodies against the nuclear antigen (EBNA) to detect a past infection.

In pregnant women with symptoms of a viral illness, EBV antibodies may be requested together with CMV and toxoplasma antibodies to help diagnose the infection. In some cases it is advisable to repeat the EBV antibody test 2-4 weeks after the first one to see whether it changes from negative to positive or to monitor any changes in antibody levels.

The VCA-IgG test, and sometimes the EBNA test, may be requested for a person without symptoms to assess whether they have been exposed to EBV in the past or are susceptible to a primary infection; this is usually recommended for teenagers and for immunocompromised patients who have been in contact with people with mononucleosis.

When is it requested?
EBV antibodies should be requested when there are symptoms of mononucleosis but the mono test is negative, and in pregnant women with “flu-like” symptoms, to identify the true nature of the infection. Symptoms may include:

• fever
• exhaustion
• sore throat
• swollen lymph glands
• an enlarged spleen and sometimes an enlarged liver

VCA-IgG and EBNA-IgG may be requested whenever the doctor wants to check for previous exposure, i.e. to identify a past infection. The tests may be repeated to assess how the antibody titre changes over time or, if the first test was negative, to check whether it later becomes positive.

What does the result mean?
If VCA-IgM antibodies are present, the patient probably has, or has very recently had, an EBV infection. If VCA-IgM antibodies are present together with the symptoms described above, mononucleosis is very likely, even if the mono test is negative. If VCA-IgG and EA-D IgG are also positive, it is extremely likely that the patient has recently had an EBV infection. If VCA-IgM antibodies are negative but the others, including EBNA-IgG, are positive, the patient has probably had a past EBV infection. If the patient has no symptoms and is negative for VCA-IgG and the other EBV antibodies, they have never been in contact with the virus and are therefore susceptible to infection. In general, rising VCA-IgG levels tend to indicate an active EBV infection, while falling levels tend to indicate a recent EBV infection that is resolving. However, treatment must be guided by interpreting changes in EBV antibody levels over time, since the level itself correlates neither with the severity of the infection nor with its duration. High VCA-IgG levels may be present and persist at that level for life.

The results are shown in the table:

The tests almost always indicate:

Is there anything else I should know?
At least two other antibodies appear during an EBV infection: an IgA antibody against the viral capsid antigen (EBV VCA-IgA) and an IgG antibody against the early restricted antigen (EA-R IgG). These antibodies can be tested as part of the diagnostic work-up of an EBV infection, but this is often not necessary.
The most common complication of mononucleosis is rupture of the spleen. Other complications of EBV infection include breathing difficulty due to swelling of the throat, a simultaneous streptococcal infection and, rarely, jaundice, skin rashes, pancreatitis and encephalitis. EBV infection is also associated with some rare forms of cancer, such as Burkitt’s lymphoma and nasopharyngeal carcinoma.

Reactivation of the virus is rare, except in patients who are significantly and persistently immunocompromised, such as those with HIV/AIDS or who have had an organ transplant. Primary infections in these patients can be more severe, and EBV-related symptoms can sometimes become chronic.

1. How is EBV infection / mononucleosis treated?
The infection is treated with rest, treatment of the symptoms and avoiding contact sports and heavy lifting for many weeks or even months to prevent a possible rupture of the spleen. No antiviral medicines or vaccines are available to speed up recovery or prevent infection.

2. Can adults get mononucleosis?
They can, but it is rare because most have already been infected at a young age and are therefore immune. When it does happen, adults less often have swollen lymph nodes and throat problems, but more often have an enlarged liver and jaundice.

3. Are EBV infection and mononucleosis found all over the world?
Yes. In less developed countries, however, mononucleosis is not common because most of the population is infected with EBV, and therefore becomes immune, in the first years of life.

4. Can EBV infection be prevented?
No, because the virus is very widespread in the population and most infected people have no symptoms but can still infect people who are not immune.

5. If I have had EBV infection, can I also get mononucleosis?
No. Once you have had an EBV infection you cannot get mononucleosis. You can, however, have similar symptoms due to another viral infection.

6. Why is mononucleosis called “the kissing disease”?
Because EBV is present in saliva and is spread by mouth-to-mouth contact; in children, contact with saliva can also happen through hands or toys that have been in someone’s mouth