Multiple Sclerosis: Late Effects of Frequent Viral Infection?

  • The Epstein-Barr virus is the leading cause of multiple sclerosis – and possibly a necessary condition, according to a new study.
  • Early vaccination could possibly protect.
  • However, the expert insists on caution.

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The suspicion has been around for a long time, but now a large US study clearly shows that the extremely widespread Epstein-Barr virus is the leading cause of multiple sclerosis. Infection with a pathogen increases the risk of developing an autoimmune disease by about 32 times, the researchers report in the journal Science. This makes the virus by far the most important cause of the disease – and possibly a necessary prerequisite.

“This job is the final piece of the puzzle,” says Klemens Ruprecht, manager of the multiple sclerosis clinic at the Mitte campus of Berlin’s Charité. “The results leave virtually no doubt as to the causation.” However, it is also clear that the vast majority of people who are infected do not develop multiple sclerosis.

Scientists have suspected the relationship for decades

Because about 95 percent of all people catch the Epstein-Barr virus (EBV) in their lifetime, which is one of the herpes viruses – usually during childhood. The infection, which is usually transmitted through saliva, is usually asymptomatic but can cause glandular fever in teens and adults – sometimes also called kissing disease or student fever because of the way it is transmitted.

The disease is accompanied by fever, fatigue, sore throat and swollen lymph nodes, but it heals in most cases.

For decades, scientists have suspected a link between EBV infection and subsequent multiple sclerosis (MS). In the case of an incurable autoimmune disease, which affects approximately 250,000 people in Germany according to the German Multiple Sclerosis Society (DMSG), the immune system in the central nervous system destroys the protective myelin sheaths surrounding the nerve fibers.

This can lead to sensory disturbances, visual impairment and mobility problems, including paralysis, which can seriously reduce the quality of life of those affected.

Blood samples tested for antibodies

Now, a team led by epidemiologist Alberto Ascherio of Harvard University has investigated the role of EBV using data from more than 10 million young American soldiers who were regularly tested for HIV between 1993 and 2013.

955 participants were diagnosed with MS while employed in the military. The researchers looked for antibodies to EBV and other viruses in blood samples taken from these patients to determine which pathogens the patients had been in contact with before the onset of the disease.

First, the researchers tested the last blood sample taken before the onset of the disease in 801 MS patients. All but one patient had antibodies to EBV, meaning they had a prior EBV infection. The time between infection and diagnosis varied considerably, averaging 7.5 years.

Risk of multiple sclerosis increased by 32

For the only patient whose blood samples did not contain antibodies to EBV, scientists still do not rule out infection with the pathogen. It is possible that the participant did not get infected until the last blood sample was taken, or that he did not develop the correct antibodies. It could also be a misdiagnosis of MS, they write.

The authors assume that infection with the virus increases the risk of multiple sclerosis 32 times. This strongly suggests that the pathogen is the cause of the disease, not just an accompanying phenomenon.

This is all the more true as the researchers also tested blood samples for antibodies to other viruses – such as cytomegalovirus, which is also a herpes virus and which, like EBV, is transmitted through saliva. The team found no connection here.

Scientists describe research as a “milestone”

The researchers write that other known factors that influence MS cannot explain the 32-fold increase in risk. The next largest risk factor, the HLA-DR15 gene variant, increases the likelihood of developing the disease threefold. The authors also consider it unlikely that there will still be unknown risk factors of the same magnitude as EBV.

“The study is a milestone,” says Ralf Gold, director of the Neurological Clinic at St. Joseph at the Ruhr University in Bochum (RUB) and chairman of the Medical Advisory Council of the German Multiple Sclerosis Society (DMSG). “You can’t ignore the results.”

Among other things, the results are in line with the data on the spread of multiple sclerosis in the Faroe Islands: After British soldiers were stationed there at the end of World War II, the number of cases increased significantly.

EBV infection necessary but not sufficient

However, the exact mechanism is unclear, as William Robinson and Lawrence Steinman of California Stanford write in the Science commentary.

“Almost everyone is infected with EBV, but only a small fraction develops multiple sclerosis,” they emphasize. “So other factors, such as genetic susceptibility, are also important in the development of the disease.” Although infection with EBV is necessary, it is not sufficient in itself to cause the disease.

Multiple sclerosis should be considered a rare late complication of EBV infection, says expert Charité Ruprecht. The current study says nothing about the mechanism. “But if we want to better understand how MS develops, that’s the main question.”

Expert: “EBV must bring about a specific change”

There are several assumptions currently circulating. This includes, for example, that the erroneous immune response against the virus ensures that the body’s defenses are directed against components of the nerve tract.

But that alone does not convince Ruprecht in light of the widespread spread of the virus: “EBV must cause a specific change in people who later develop multiple sclerosis, drop the molecular switch,” the neurologist suspects.

This change supposedly affects the B cells of the immune system. There are many indications that these B cells are involved, particularly the fact that the virus infects these cells and stays there for life.

B lymphocytes are assigned a central role

This suspicion is further supported by a relatively new therapy: antibodies directed against CD20, a protein found on the surface of these B cells. The antibodies kill such B cells in the peripheral blood. “This therapy is very effective and shows that B cells play a key role in MS,” emphasizes Ruprecht.

Scientific commentators Robinson and Steinman write that several studies have identified EBV infected B cells in the brains of MS patients. They also relate to the efficacy of the CD20 antibodies: “The significantly improved B cell degradation effect in MS clearly demonstrates that B cells play a key role in the pathophysiology of the disease.”

At the same time, they point to two weaknesses of the therapy: on the one hand, the antibodies could not cross the blood-brain barrier in sufficient quantities. Moreover, they did not reach B cell precursors that lack CD20.

Vaccination against Epstein-Barr virus? The expert recommends caution

That’s why Harvard’s Ascherio team insists that to protect against multiple sclerosis, you should target Epstein-Barr virus directly, for example through vaccination. “The very low risk of MS in people without EBV suggests that the vast majority of MS cases are caused by EBV and can be prevented with adequate vaccination,” they write.

In addition, vaccination may also protect against EBV-related cancers such as Hodgkin’s lymphoma and Burkitt’s lymphoma.

However, the vaccine is not yet visible. And Ruprecht basically insists on caution: “Vaccination with EBV would be the best solution to prevent multiple sclerosis – but only if it reliably and permanently protects against infection.”

Even in this case, it was decades before it was finally clear whether such a vaccine actually protects against MS.

Vaccinations can be counterproductive

However, if the vaccine does not prevent EBV infection but only delays it, vaccination may even be counterproductive, explains Ruprecht. The later in life a person becomes infected with the Epstein-Barr virus, the greater the risk of developing glandular fever – as well as multiple sclerosis.

“Paradoxically, if EBV vaccination during infancy prevented infection for as little as 10 to 20 years, it could actually increase the incidence of multiple sclerosis.” (ff / dpa)


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