Berlin – A herpes virus that remains in the human body for life following infection and a disease of the central nervous system whose cause is not fully understood: For decades, researchers have suspected a connection between the Epstein-Barr virus (EBV) and multiple sclerosis (MS) – well might American scientists in a study published in the journal Science show that an infection with the widespread pathogen increases the risk of the autoimmune disease by a factor of regarding 32. Such a high risk factor is known, for example, in the connection between smoking and lung cancer, commented Henri-Jacques Delecluse, head of the working group on the pathogenesis of infection-related tumors at the German Cancer Research Center (DKFZ) in Heidelberg.
In Europe, according to the MS barometer, the European Multiple Sclerosis Platform 1.2 million people with MS. In Germany, the number is estimated at around 252,000. In the case of the chronic inflammatory disease, which has not yet been cured, the body’s own immune system attacks the nerve cells and the protective insulating layer of the nerve fibers (myelin). They are uncovered and the signals that travel along the nerve fibers from the brain via the spinal cord to muscles and organs are slowed down or blocked. This leads to neurological disorders such as tingling in the hands and feet, movement problems, paralysis, visual impairment, concentration problems, dizziness or the fatigue syndrome. MS varies so much from patient to patient in terms of course, symptoms and therapeutic success that it is known as the “disease with 1000 faces”. MS occurs in regarding eight out of ten patients between the ages of 20 and 40.
There is still no explanation as to why some people develop MS and some do not. In the current Science study, the team led by epidemiologist Alberto Ascherio from Harvard University examined the role of the Epstein-Barr virus using data from more than ten million members of the US army who had been routinely examined for HIV for 20 years . 955 of them were diagnosed with MS while on duty. The researchers looked for antibodies once morest EBV and other viruses in the blood samples kept from these patients in order to determine which pathogens the patients had been in contact with before the onset of the disease.
About 95 percent of all people become infected with EBV, mostly in childhood. The infection, which is usually transmitted via saliva, is usually asymptomatic, but can cause glandular fever in adolescents and adults – because of the way it is transmitted, it is also called kissing disease or student fever. The disease is accompanied by fever, fatigue, sore throat and swollen lymph nodes, but in most cases it heals.
Other viruses do not increase the likelihood of MS
First, the researchers working with Ascherio examined the last blood sample taken before the onset of the disease in 801 of the MS patients. All but one patient had antibodies to the herpes virus, meaning they had had a previous EBV infection. The mean time between infection and diagnosis was 7.5 years.
The scientists were also able to show that in people who were originally EBV-negative, no biomarkers for MS were initially detectable either, but these then became detectable in blood samples following EBV infection before the onset of MS symptoms. This strongly suggests that the pathogen is a cause of the disease – and not just an accompanying phenomenon.
This finding is all the more valid as the researchers also examined the blood samples for antibodies of the cytomegalovirus, which is also one of the herpesviruses and is transmitted through saliva in a similar way to EBV. The team found no connection here.
Mechanisms not understood
“The strength of the paper lies in the very large number of over ten million people observed and in the length of the study of around 20 years. This makes it the most compelling study in the field to date and clearly shows that without EBV infection, MS would almost never develop,” said Delecluse. “The current work provides further convincing arguments that the connection between EBV and MS is actually causal, which means that MS almost never develops without a previous EBV infection,” said the head of the multiple sclerosis outpatient clinic on campus Center of the Berlin Charité, Klemens Ruprecht. “The results leave practically no doubt as to a causal relationship.”
However: The mechanisms by which the Epstein-Barr virus contributes to the development of multiple sclerosis are not known. Even if an infection with EBV is a necessary prerequisite for the development of MS, it is important to point out that by no means every person infected with EBV develops MS, added Charité expert Ruprecht. MS might be considered a rare late complication of EBV infection. The central scientific question that needs to be addressed is not whether, but how EBV is involved in the development of MS.
“Almost everyone is infected with EBV, but only a small fraction develops MS,” emphasize researchers William Robinson and Lawrence Steinman from Stanford University in California in a Science commentary. “So other factors such as genetic susceptibility are also important for the development of the disease.” An EBV infection is indeed necessary, but not sufficient on its own to cause the disease.
Epstein-Barr virus specifically affects B cells
There are currently a number of assumptions circulating. This includes, for example, that a misguided immune response once morest the virus ensures that the body’s defenses are directed once morest components of nerve tracts. But that alone does not convince Ruprecht in view of the widespread spread of the virus: “EBV must cause a specific change in people who later get MS, flip a molecular switch,” suspects the neurologist.
This change presumably affects the B memory cells of the immune system. In the current study, there are various indications that these B cells are involved: above all, the fact that EBV infects the B cells and remains in these cells for life.
The suspicion is further supported by a relatively new therapy: antibodies directed once morest CD-20, a protein on the surface of these B cells. The antibodies kill such B cells in the blood. “This therapy is very effective, demonstrating a central involvement of B cells in MS,” said Ruprecht. “So it’s conceivable that the effectiveness of these therapies is related to the fact that EBV specifically infects B cells.”
Ascherio’s Harvard team writes that to protect once morest multiple sclerosis, one must target the Epstein-Barr virus directly, for example through vaccinations. The US pharmaceutical company Moderna announced last week that it would start clinical trials of a vaccine once morest the Epstein-Barr virus in humans.
Ruprecht said: “An EBV vaccination would be the ultimate solution to prevent multiple sclerosis – but only if it reliably and also permanently protects once morest infection.” Even in this case it would take decades before it was finally clear whether such a vaccine actually protects once morest MS. Henri-Jacques Delecluse from the DKFZ agrees that if EBV infection might be completely prevented, the frequency of MS should fall accordingly. However, it is believed that current vaccinations once morest the Epstein-Barr virus might potentially reduce the symptoms of the infection, such as mononucleosis, but would probably not completely prevent long-term EBV infection. “In this respect, it is currently unclear whether an EBV vaccination can prevent MS.”
Genes and environmental factors as a cause of MS
When asked to what extent an EBV infection can be seen as the main cause of MS, Roland Martin, group leader of neuroimmunology and multiple sclerosis at the University Hospital Zurich, warned of caution: “You might draw this conclusion from the results, but I feel a little concerned regarding it too far.” The past 20 years of data on the cause of MS have suggested that there is a complex genetic background that predisposes to MS. “In addition to an EBV infection in connection with MS, a number of other environmental risk factors should also be mentioned: low vitamin D, smoking, obesity in late childhood or early adulthood, shift work or a disturbed day-night rhythm at this age, and certain intestinal bacteria.” , he explained. Researchers also believe that multiple sclerosis is more common in temperate climates, including Europe, New Zealand or the northern United States. There are also gender-specific differences in MS: women are affected two to three times more often than men. Apparently, hormones also play a role in the disease – exactly which ones, one does not know.
The environmental factors are probably more important at the level of the individual factor than individual genes, according to the Swiss neurologist Roland Martin. “In my opinion, the study cannot conclusively clarify whether EBV is the most important environmental factor or one of several.”
Groups and regulars’ tables in Berlin
In Berlin there are many self-help groups and regulars’ tables for people with MS or their relatives. For example, the women’s group FGMS for people between 40 and 60, which meets in Wilmersdorf on the first Tuesday of every month. Or a group for newly affected people, which is organized twice a month by the German Society for Multiple Sclerosis (DMSG) Berlin. A comprehensive list of other groups can be found at Homepage of the DMSG Berlin.
The state association also has a wide range of advice, including finding medical specialists or financial aid. There is also information on nutrition, family planning and sport. MS Connect is the DMSG’s exchange platform for people with MS, where members can get to know other MS sufferers from the region.
Because MS is still not understood today, there is no cure, existing foci of infection in the brain and spinal cord cannot be reversed. The only possibility is to use a therapy to keep the immunologically mediated damage as small as possible by interfering with the immune system. You can also take therapeutic action to prevent new inflammation from developing.
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