A growing body of evidence suggests the main driver of MS is an abnormal immune response to Epstein-Barr virus.
An estimated 2.8 million people worldwide have multiple sclerosis (MS). This autoimmune condition is the result of the immune system damaging parts of the nerves in the brain and spinal cord, which can lead to problems with movement, vision, balance and sensation.
While many MS symptoms can be managed, there’s currently no way to cure or prevent the condition. This is due to the complex immune response that leads to this disease. But a blood test recently developed by me and my colleagues has allowed us to estimate the strength of the immune response in people with MS.
This finding may not only bring us one step closer to understanding the causes of MS, but to developing better treatments for the condition.
Researchers still aren’t entirely sure what exactly causes MS. But a growing body of evidence suggests the main driver of the condition is Epstein-Barr virus (also known as glandular fever or infectious mononucleosis).
Epstein-Barr virus (EBV) is spread through saliva and typically infects children at a young age. Symptoms are often mild, resembling the common cold. But for others they may have a sore throat and high levels of fatigue.
However, the body never actually clears the virus. In most people, the immune system renders it harmless. But people with MS have an abnormal immune response to this virus – which may be responsible for the disease.
The link between Epstein-Barr virus and MS has been considered for over 20 years, with multiple studies highlighting the high prevalence of this virus in people with MS. But in 2022, a large study of more than 10 million young adults finally provided a robust, epidemiological basis for this link.
The study, which followed participants for 20 years, found that risk of MS increased 32-fold after an EBV infection. No other viral infections were shown to increase MS risk.
Work has also shown that the proteins which comprise EBNA-1 (a component of Epstein-Barr virus) and myelin (the outside coating of our nerves), share a similar structure. Myelin normally keeps our nerves healthy, but in people with MS the immune system recognises myelin as a foreign invader and attacks it.
This finding provides an important starting point for research investigating the mechanisms behind the aberrant immune reaction that leads to MS. It may also allow researchers to some day develop better treatments for MS.
MS symptoms are typically managed using immunosuppressive drugs. These suppress the body’s overall immune response, which can reduce the severity of MS symptoms.
But these drugs have many unwanted side-effects, including headaches, stomach pain and gastrointestinal problems. And, because they modify the immune system’s response, this can result in more frequent chest, sinus or bladder infections.
Antiviral drugs could be another possible treatment route. These target a specific virus in the body and prevent it from replicating. Because these only target one specific virus, they don’t dampen the body’s overall immune system.
There have been a series of intriguing case reports of people with MS who also developed HIV and were given antivirals – a standard part of HIV care, as they stop the virus replicating itself.
The surprising consequence was that these people’s MS symptoms appeared to resolve. This suggests antivirals could be a useful treatment. By preventing EBV from replicating in the body, it could help put MS into remission.
But in order to develop an antiviral, we need to know just how strong of a response the immune system is mounting against EBV in patients with MS.
With this in mind me and my colleagues developed a blood test that quantifies the body’s immune response to EBV.
To test if it worked, we took blood samples from people with MS, epilepsy and those with no existing medical conditions. We looked at 145 people in total and also confirmed with laboratory testing that each person had signs of previous EBV infection.
Although our main focus was MS, we wanted to compare how these participants’ immune responses differed compared to people with no existing health conditions, and against people with a different neurological condition that isn’t linked to EBV.
We found that the immune response to EBV was higher in people with MS than it was in people from either of the two other groups. This provides support for the idea that it is the immune response to EBV that is responsible for causing MS.
We also saw that current MS drugs do influence the immune system’s response to EBV. Drugs that deplete circulating immune cells (known as B cells) were shown in MS patients to create an immune response to EBV that was equivalent to the immune response healthy participants had to the virus.
We were interested in this result as the precise mechanism of action these B cell depleting drugs have in MS has not been understood. One theory has been that these drugs clear EBV from the system by attacking the B cells that the virus hides behind. It has been difficult to prove this, but we believe our study’s finding support this theory.
One of the leading aims of our study has been to develop a potential way to record the effect of drugs that target EBV in MS in clinical trials. We believe that testing for virus levels alone would not suffice, as the disease is caused by an immune response. We believe our new blood test has the potential to be used in future clinical trials using antivirals or vaccines against EBV in MS.
Hugh Kearney receives funding from Science Foundation Ireland
