Why do antibodies to Pfeiffer's disease (EBV) sometimes stay positive for years?

Prolonged positive EBV antibodies without active infection may indicate an abnormal immune response or underlying health problems.

Epstein-Barr virus (EBV), the causative agent of Pfeiffer's disease, is a common virus that often leads to an infection with symptoms such as fatigue and sore throat. Normally, after an infection with Pfeiffer's disease, your body develops antibodies to fight the virus. These antibodies, known as IgM and IgG, help identify a recent or previous infection. What can be confusing, however, is when these antibodies remain positive for years without an active infection. This phenomenon raises many questions, especially for people who have been struggling with unexplained health symptoms, such as Long COVID, for a long time.

A question from Marcel: How is this possible?

On July 13, 2024 Marcel asked the following question, "How can it be that I have been testing positive for all three immunoglobulins (IgM, IgG, and IgA) against Pfeiffer's disease for six years in annual tests? It is said that IgM can basically be a "false-positive," but six years seems very strange to me. Also, an EBV PCR test was done once and it gave a negative result. How is this possible?"

What do the tests mean for Pfeiffer's disease?

In a standard serological test for Pfeiffer's disease, different types of antibodies are measured:

1. IgM antibodies: These are usually associated with a recent or active infection. With a new infection, the body will produce IgM to fight the virus. Normally, these antibodies disappear within a few months.
2. IgG antibodies: These usually remain present for life and are indicative of a previous infection. They keep the body protected from future infections.
3. EBNA IgG antibodies (Epstein-Barr nuclear antigen): These antibodies appear several months after the initial infection and then remain present for a long time, also indicating a passed infection.

What does it mean if these antibodies remain positive for years?

When you get positive test results for both IgM and IgG for years, as Marcel describes, this indicates an unusual situation. Here are some possible explanations:

1. No active viral replication:
• Despite the continued presence of IgM and IgG, a negative PCR test, as is the case with Marcel, indicates that active viral replication is not taking place. This means that the virus is no longer actively present in the blood, but your immune system may continue to respond as if it were.
2. Chronic immune response or dysfunction:
• A prolonged positive IgM test is unusual and may indicate a chronic or abnormal immune response. This may be due to an underlying condition, such as autoimmune disease or chronic fatigue syndrome (CFS). In these conditions, the immune system remains activated for long periods of time, even without an active infection.
3. False-positive IgM results:
• Another possibility is that the IgM test gives false-positive results. This may occur because of cross-reactivity with other proteins in the blood or because of the presence of rheumatoid factor, which sometimes interferes with serologic testing. It is indeed possible, as Marcel wonders, that six years of positive IgM results indicate a false-positive reaction, but it is very unusual and should be investigated further.
4. Relationship to Long COVID:
• It is notable that people with Long COVID also often have elevated antibodies to Pfeiffer's disease for long periods of time. Although much research is still needed, there may be a link between the persistent immune activity in Long COVID and a previous EBV infection. It is possible that the prolonged recovery after COVID-19 causes the immune system to continue to respond abnormally to old viral antigens, such as those from the virus that causes Pfeiffer's disease.

Additional tests to identify the cause

If, like Marcel, you have long-term positive IgM antibodies to Pfeiffer's disease, there are several additional tests that can help explain the cause:

1. Comprehensive autoantibody profiles:
• Tests such as ANA (antinuclear antibodies) and anti-dsDNA can help rule out autoimmune diseases, such as lupus, which can cause an abnormal immune response.
2. Cytokine profile:
• Measuring cytokines, such as interleukins and tumor necrosis factor (TNF), can provide insight into the level of inflammation and immune activation in your body.
3. B-cell and T-cell phenotyping:
• This test examines the composition of your immune cells and can help detect abnormalities in your immune system, such as increased activation of B cells responsible for antibody production.
4. Repeated PCR testing for EBV:
• Although previous PCR tests were negative, repeated testing at different times can help rule out intermittent or latent viral reactivation.
5. Tests for other chronic viral infections:
• Since cross-reactivity may occur, it may be useful to test for other chronic viruses, such as cytomegalovirus (CMV) or herpes simplex virus (HSV), which may potentially elicit a similar immune response.
6. IgM subclass determination:
• Examining specific subclasses of IgM can help determine whether there is an unusual IgM response or a problem with immune regulation.
7. Functional immune testing:
• Tests such as lymphocyte proliferation assays can provide insight into how well your immune system is functioning and can identify specific defects in the immune response.

What can you do if you have long-term positive test results for Pfeiffer's disease?

If you have been dealing with positive tests for Pfeiffer's disease for an extended period of time with no clear explanation, such as Marcel's, it is important to have it investigated further. A specialist, such as an immunologist or infectiologist, can perform additional tests to determine the cause of the persistent immune response. This can also help identify any underlying conditions, such as autoimmune diseases.

In addition, it is wise to repeat the tests in another laboratory to verify that the results are consistent. Eliminating laboratory errors can help you get a clearer picture of your health status.

In brief

The combination of prolonged positive IgM, IgG and EBNA-IgG antibodies to the virus causing Pfeiffer's disease, without detectable viral DNA, does not indicate an active infection, but rather an abnormal or chronic immune response. This may indicate an underlying immune dysfunction or another health condition that requires further evaluation and treatment. Especially in people with Long COVID, there appears to be a possible link between persistent antibodies to Pfeiffer's disease and long-term symptoms, suggesting that the immune system plays an important role in the recovery process.

By proactively looking for the causes of these persistent positive test results, you can get a better handle on your health and find the right treatment.