Antibody test – mononucleosis (EBV – Epstein-Barr virus)

Infectious mononucleosis, commonly referred to as the “kissing disease,” is caused by the Epstein-Barr virus (EBV), a member of the human herpesvirus family (1). The clinical presentation of the disease is variable and may be asymptomatic or may present with symptoms similar to angina (fever, swollen lymph nodes, sore throat, fatigue, loss of appetite, and whitish tonsil plaques) (2). Mononucleosis is most often diagnosed based on clinical presentation, complete blood count with differential, liver function tests, specific antibodies to EBV, and abdominal ultrasonography.

Why should I undergo serological testing for antibodies to infectious mononucleosis?

Serological testing measures antibodies to the viral capsid antigen, anti-VCA IgM and IgG, and antibodies to the nuclear antigen, anti-EBNA (4). In practice, the determination of anti-VCA IgM and IgG antibodies and anti-EBNA IgG (4) is used, which is advantageous mainly for the following reasons:

1. Determination of antibodies to EBV is important to confirm infection, to determine whether an individual has previously had infectious mononucleosis or is susceptible to EBV infection (2) (3).
2. Testing for antibodies to EBV is recommended for symptoms of infectious mononucleosis if the rapid monotest is negative (5).

When is it appropriate to perform a serological test for antibodies to mononucleosis?

The clinical picture of mononucleosis is variable, as it can be a) asymptomatic, b) with symptoms typical of infectious mononucleosis, or c) rarely with very severe symptoms (2). The first symptoms appear approximately four to six weeks after infection with Epstein-Barr virus, may develop very slowly, and may not all appear at the same time (6). In children and adolescents, mononucleosis is “confused” with tonsillitis due to symptoms such as fever, extreme fatigue, sore throat and headache, swollen lymph nodes in the neck and armpits, and white-gray necrotic plaques on the tonsils (4).

The liver and spleen are enlarged in at least 50% of cases. In some cases, the liver, spleen, or both remain enlarged long after the fatigue has subsided. While most recover within two to four weeks, some may experience extreme fatigue for several weeks after starting treatment. Occasionally, symptoms of infectious mononucleosis may persist for more than six months (6). In adults, a subacute course is more typical, with symptoms such as a mildly elevated temperature (not reaching fever level), malaise, enlarged lymph nodes, and an enlarged liver and spleen; these persist for several months (4) (2).

Complications are rare but can be more serious. Liver involvement is typical, with liver function tests being two to three times higher than normal. Less commonly, lung involvement or a reduced red blood cell count are seen (4) (5) (1).

What should you know about infectious mononucleosis before undergoing serological testing?

Serological testing for antibodies to specific EBV antigens can be helpful in diagnosing infectious mononucleosis (4).

- Antibodies to viral capsid antigen (anti-VCA) IgM and IgG

IgM anti-VCA appears early in EBV infection and usually disappears within four to six weeks, while IgG anti-VCA appears in the acute phase of EBV infection and peaks two to four weeks after the onset of symptoms, then declines slightly and then persists throughout life. Everyone who has had EBV infection has anti-VCA IgG antibodies (7).

- Antibodies to early antigen (anti-EA) IgG

Anti-EA IgG appears in the acute phase of the disease and generally declines to undetectable levels after three to six months. The detection of anti-EA antibodies is a sign of active infection in many individuals. However, in approximately 20% of healthy individuals, anti-EA antibodies can be detected even years after EBV infection (7).

- Antibodies to EBV nuclear antigen (anti-EBNA)

Anti-EBNA is determined by conventional immunofluorescence and is not present in the acute phase of EBV infection. They appear slowly, usually about two to four months after the onset of the first symptoms, and persist throughout life. In a small part of the population, they may not develop at all. The absence of anti-EBNA in the presence of EBV-VCA-IgM positivity indicates a primary (new, current) EBV infection (EBNA IgG antibodies are used to distinguish primary infection from reactivation) (7) (8).

- Monospot test

Some laboratories also offer the so-called monospot test, but according to experts, it is not suitable for widespread use. The antibodies detected by the Monospot test may be associated with other disease states such as infectious mononucleosis. Studies have shown that Monospot sometimes provides false positive or negative results and cannot confirm the presence of EBV infection ( 7).

What´s measured

About EBV and infectious mononucleosis

Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a herpesvirus found only in humans. Serological testing for the presence of antibodies to EBV is not usually necessary to diagnose infectious mononucleosis, but may be useful in the following cases:

a) when the patient does not have typical symptoms of infectious mononucleosis,

b) when he has an illness caused by EBV infection, but it is not mononucleosis,

c) to determine susceptibility to EBV infection

d) to verify whether the individual has previously had infectious mononucleosis (7).

The virus persists in the body throughout life and can reactivate at any time with a slightly different clinical picture, especially in cases of weakened immunity, chronic illness or prolonged stress. Almost everyone comes into contact with EBV during their lifetime. In countries with high hygiene standards, the first wave of contact with the virus occurs around the age of five, the second wave occurs in adolescents and young adults. In adulthood, 90 to 95% of the population has antibodies to EBV (1) (4) (7) (8).

Infectious mononucleosis occurs mainly in children and adolescents. Its incidence decreases with increasing age. The source of infection is a sick individual or a carrier of the virus who has no obvious symptoms. Transmission occurs by droplet infection, direct contact, or saliva (e.g., kissing). The upper respiratory tract is the gateway through which the virus enters the body. There is currently no vaccination against infectious mononucleosis, as there is no approved vaccine (9) (4) (3). Interpretation of test results should always be done in combination with clinical information about the patient.

Susceptibility to infection

In the absence of IgG antibodies to EBV-VCA, the subject is considered susceptible to EBV infection (7).

Primary (active) infection

Active infection is characterized by the presence of anti-VCA IgM and the absence of EBNA antibodies (at least four weeks after the onset of symptoms). The disease may resolve before diagnostic antibody levels appear. Rarely, EBV-specific antibodies are not detectable in individuals with active infection (7).

Past infection

Previous infection is characterized by the presence of antibodies to VCA and EBNA (months to years ago) (7).

Interpretation of results

In case of purchasing the interpretation of the results, this interpretation is created by an internist from uLékaře.cz.