Does EBV cause MS?
The cause of MS is not entirely clear, but it’s likely a mixture of genetics, environment and lifestyle factors. It is difficult to say whether something definitively causes MS, or whether a combination of different factors increases the risk of developing MS. An important new study strengthens the evidence suggesting the Epstein-Barr Virus (EBV) could be one of those risk factors.
What is EBV?
EBV is a type of herpes virus. It is one of the most common viruses, found in 9 out of 10 people across the globe. It is transmitted through bodily fluids such as saliva. It can cause infectious mononucleosis, also known as glandular fever. After the body recovers from illness, EBV stays ‘silent’ in the body – creating a lifelong hidden infection.
How does EBV relate to MS?
After the human body has fought a virus, the immune system leaves parts of the invader behind –known as antigens. The body recognises the antigens and stimulates production of antibodies, to help the immune system recognise the virus if it invades the body again. EBV antibodies have been linked to several cancers and autoimmune diseases, including MS. Studies suggest hidden EBV antibodies may interact with the immune system and the nervous system, giving rise to disease.
Various studies have found a link between EBV and MS, with up to 99% of people with MS found to have antibodies against EBV. Equally, most people with no EBV antibodies tend to not develop MS.
What does the new research show?
Professor Alberto Ascherio and colleagues from the Harvard T.H. Chan School of Public Health in Cambridge, USA, followed 10 million US military personnel over 20 years. They wanted to see if EBV infection increases the risk of developing MS.
At the beginning of the study, they took blood samples from everyone and measured antibodies against EBV to see if individuals had been infected by EBV in the past. They then took blood samples every other year, to test if previously uninfected people became infected with EBV. The group also measured the level of Neurofilament Light (NfL). NfL is a biomarker – something that can tell us about the state of a disease. NfL is often found in the blood of people who have had some form of brain or nervous system damage, such as when myelin breaks down in MS. In people who go on to develop MS, the level of NfL in the blood is high up to six years before MS symptoms develop. Ascherio and colleagues found that in people with MS, NfL only increased after EBV infection. This led the researchers to believe the EBV infection came before MS started.
From the 10 million people studied, 801 were diagnosed with MS, out of which 800 people had EBV antibodies. They found that the overall risk of developing MS increased 32-fold after infection with EBV. The group also studied other viruses, such as the as cytomegalovirus (CMV), another common human virus. They did not find any change in the risk of developing MS after infection with CMV.
The high level of increased risk in people infected with EBV, together with the large number of people studied, strongly indicates that EBV may be an important risk factor in developing MS.
What do these results mean for people affected by MS?
These results suggest that EBV antibodies are linked to an increased risk of developing MS. But, as most people who are infected with EBV do not develop MS, EBV is not enough to cause MS on its own. We now need to understand why some people who have been infected with EBV develop MS, while others do not.
There is a delay of about ten years between when EBV antibodies are detected and the onset of MS symptoms. It is unclear why this is the case, but mounting evidence suggests that there is an early phase of MS called the prodromal phase. In this phase, MS is believed to be developing in the body despite the person not experiencing typical MS symptoms. During this time, EBV antibodies may already be slowly fighting the defences of the immune and nervous systems.
Because there is no way to avoid EBV infection, vaccination against EBV may be the answer. And if EBV is a risk factor for MS, it may be possible to develop an EBV vaccine to prevent MS. There are many researchers currently investigating EBV vaccines, as well as treatments that target EBV in people who already have MS. The pharmaceutical company Moderna started a Phase I trial of a potential EBV vaccine in January 2022, testing its safety in healthy volunteers. We won’t know the results of these studies for some time, but the outcomes will have important implications for future prevention and treatment of MS.