Viruses are warned. This notice can claim general validity, after two years of the pandemic it is particularly relevant. In this respect, the statement by researchers from Harvard, according to which an infection with the Epstein-Barr virus (EBV) significantly increases the risk of multiple sclerosis (MS), is certain to attract attention. neurologists, immunologists and epidemiologists put in the trade magazine Science a relevant study.
Multiple sclerosis is a chronic inflammatory disease of the central nervous system. This attacks the protective myelin sheaths in the brain and spinal cord, which cover the nerve fibers, which gradually affects the nerve function. In order to research the possible connection between viral disease and nerve destruction, Alberto Ascherio’s team was able to fall back on data from ten million adults who took up service in the US Army between 1993 and 2013. Since military personnel are tested for HIV every two years, extensive blood samples were available. These showed that almost 95 percent of the men and women had antibodies against EBV, i.e. had already been infected with the virus that can lead to glandular fever. The disease is also known as infectious mononucleosis and – because it is so contagious – in English as “kissing disease”.
Of the army employees, 955 developed multiple sclerosis over the years. In 35 of the patients, no antibodies against EBV could be detected in the first blood sample – they were not infected with EBV at the time the sample was taken and were therefore seronegative. However, before the onset of MS, 34 of the 35 people became infected with the virus and developed antibodies to EBV. In addition, the researchers found biomarkers for MS in blood samples from those subjects who were initially EBV-negative – degradation products of neurofilaments that suggest a degeneration of nerve tracts, as is typical for MS. Initially, these biomarkers could not be discovered, but after the EBV infection they could be detected in blood samples before the first MS symptoms set in.
From these data, the researchers conclude that infection with EBV increases the likelihood of developing multiple sclerosis by a factor of 32, while the risk after other viral infections does not increase, as the scientists showed with antibody tests for other viruses. “The hypothesis that EBV causes multiple sclerosis has been explored by our and other groups for years, but this study provides the first evidence of causality,” says Ascherio. “This is an important step because it suggests that most MS cases could be prevented by ending EBV infections.” In addition, combating EBV could lead to the discovery of a therapy for MS.
Dozens of genetic and environmental factors play a role in addition to infection
Despite the amount of data from the long-term study, unanswered questions remain. After all, more than 90 percent of people will become infected with EBV in their lifetime, but few will subsequently develop MS, although the virus remains in the body for life. “The data suggest a correlation between EBV infection and MS, which makes causality probable but cannot prove it,” says Wolfgang Hammerschmidt from the German Center for Infection Research. “The study makes it very likely that EBV infection is a prerequisite for MS. But is EBV also the cause or driver of MS? The study cannot answer that.”
The conclusion that EBV infection is the main cause of multiple sclerosis goes too far, even for other experts. “The data from the past 20 years on the cause of MS indicate that there is a complex genetic background that predisposes to MS,” says neuroimmunologist Roland Martin, who researches multiple sclerosis at the University Hospital Zurich. “There are a number of risk genes. In addition to EBV infection, there are other environmental risk factors associated with MS.” These include low vitamin D levels, smoking, obesity in late childhood and early adulthood, a disturbed circadian rhythm at this age, and certain gut bacteria. “In addition, a symptomatic EBV infection – glandular fever, which occurs with infections after puberty and in early adulthood – increases the risk significantly, by a factor of about seven,” says Martin. “In my opinion, the study cannot conclusively clarify whether EBV is the most important environmental factor or one of several.”
Experts welcome vaccination against EBV. “Theoretically, the causal relationship between EBV and MS means that vaccination against EBV should prevent the development of MS,” says Klemens Ruprecht, head of the MS outpatient clinic at the Berlin Charité. “However, there are practically no EBV vaccines currently available. In addition, it would be decades before it would be clear whether such a vaccine actually offers protection against MS.”