2023-05-22 11:32:00
The cause of multiple sclerosis (MS) has not yet been finally clarified. Environmental influences play a role, but genes also play a role. Infectious diseases are also associated with MS. But what exactly is the connection? Are they warning signs or triggers? Studies have examined this.
Hollywood actress Christina Applegate or the German ex-competitive athlete and presenter Anna Kraft are two famous sufferers: According to the “Deutsche Multiple Sclerose Gesellschaft Bundesverband eV”, an estimated 280,000 people in Germany are currently suffering from the inflammatory disease of the central nervous system. 15,000 new diagnoses are added every year. Unfortunately, the causes have not yet been clearly defined. Both genes and external influences, such as viral infections, can play a role.1 A study from 2021 was able to show that infection with the Epstein-Barr virus increases the risk of MS.2 Now a new study uncovered the more precise connection between glandular fever and multiple sclerosis.
Mononucleosis and multiple sclerosis
Mononucleosis has long been suspected of increasing the risk of multiple sclerosis. For example, a blood test from 2017 with 1090 Americans of different ethnicities (“Blacks”, “Hispanics”, “Whites”) revealed this.3 Researchers from Sweden found that infections at a young age, namely between eleven and 19 years of age, seem to be associated with later MS disease. These included infections of the central nervous system, infections of the respiratory tract and glandular fever. The risk of MS appears to be particularly increased when the infectious diseases have had a severe course that has required patients to be hospitalized.4
The same Swedish scientists then focused on mononucleosis as a risk factor in the study from 2021 mentioned at the beginning. What the previous studies could not answer was how exactly the connection between fever and MS looks like. It could have been argued that it is rather the genes that trigger MS and also make those affected more susceptible to infectious diseases.
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Study with siblings
In order to clarify whether infections such as glandular fever increase the risk of multiple sclerosis and can be a trigger of the disease, the research team led by Scott Montgomery examined sibling pairs who, due to their close relationship, share a large part of their genetic makeup and grew up similarly.
The scientists assumed that if only one person in a sibling pair had the infection and later developed MS, while the other person did not develop the fever and did not develop MS, this would indicate that the infection caused multiple sclerosis – and fewer the genes. However, if the sibling who did not have glandular fever also develops multiple sclerosis as an adult, this indicates that the genes and not the infection are the risk factor. The more families with sibling pairs show the former pattern, the more certain it is that mononucleosis is an MS trigger.
Also interesting: Epstein-Barr virus – take it easy after glandular fever
Almost 2.5 million Swedes took part in the study, 6,000 of whom had been diagnosed with multiple sclerosis after the age of 20. The researchers compared the MS disease with the occurrence of mononucleosis in childhood (0 to 11 years), adolescence (11 to 19 years) and young adulthood (20 to 24 years). The analysis first compared the siblings within a family before all the results were then combined.
Mononucleosis in teens increases the risk of multiple sclerosis
In fact, the study was able to show that mononucleosis – and thus other infections – can almost certainly cause MS. The scientists were also able to confirm again that the age of the infectious disease plays a role. Study participants who contracted glandular fever as young adults did not show an increased risk of MS. The likelihood of developing multiple sclerosis is apparently increased if you contract glandular fever as a child or adolescent. According to the analysis, the risk is highest when the infectious disease occurs after the age of eleven and before the age of 20.
Also interesting: Infections that affect children particularly often
What happens in glandular fever in the body that can lead to MS?
But why can viral diseases such as glandular fever be to blame for someone developing MS many years later? Knowing that there is a connection does not explain what exactly is going on in the body of those affected. A new study, also from Sweden, got to the bottom of this. To do this, researchers at the Karolinska Institute analyzed and compared blood samples from 713 MS patients with those from 722 healthy people.5
Misdirected antibodies could trigger multiple sclerosis
The scientists discovered misdirected antibodies in the brain and spinal cord. Since MS is a disease in which the immune system attacks nerve fibers in the brain and spinal cord, the researchers conclude that the said antibodies, which are produced due to glandular fever, could be responsible for the increased risk of MS.
The detected antibodies are those called EBNA1. This is not uncommon at first, as they are made in the body in response to an infection to fight it. What was remarkable, however, was that the researchers were able to demonstrate that the antibodies can also bind to so-called CRYAB proteins. These proteins are found in the brain and spinal cord and are tasked with protecting the body from the harmful effects of inflammation. However, if the EBNA1 antibodies bind to these proteins and migrate to the brain and spinal cord, they could subsequently damage the nervous system and lead to MS symptoms of fatigue, balance and mobility problems. A mechanism that experts call cross-reactivity.
The misdirected antibodies were detected in about 23 percent of MS patients and only 7 percent of healthy people. The study also provided evidence that infections such as glandular fever could also lead to cross-reactivity with T cells that promotes MS. In other words, with cells that are involved in the formation of antibodies to fight the disease in the event of infections.6
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Conclusion
Multiple sclerosis is still an elusive disease. Due to its very different symptoms and progression, it is also known as the “disease with 1000 faces”.7 And as far as the causes and triggers are concerned, much is still uncertain. However, the current state of research seems to indicate that certain severe infections at a young age may play a greater role in the onset of MS than previously thought.
Sources
- 1. German Multiple Sclerosis Society Federal Association eV (dmsg). What is multiple sclerosis? (accessed on May 22, 2023)
- 2. Montgomery S, Xu Y, Hiyoshi A et al. (2021). Association of Infectious Mononucleosis in Childhood and Adolescence With Risk for a Subsequent Multiple Sclerosis Diagnosis Among Siblings. JAMA Network Open.
- 3. Langer-Gould A, Wu J, Lucas R et al. (2017). Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study. Neurology
- 4. Montgomery S, Xu Y, Hiyoshi A et al. (2021). Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis. Brain
- 5. Thomas, OG, Bronge, M., Tengvall, K. et al. (2023). Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis. Science Advances.
- 6. German Center for Infection Research. T cells. (accessed on May 22, 2023)
- 7. WWU Munster. The disease with 1000 faces: Good therapies for multiple sclerosis. (accessed on May 22, 2023
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