- There is currently no blood test to detect MS before symptoms arise
- A new test found antibodies to an Epstein-Barr virus (EBV) protein rise years before MS onset and predict MS diagnosis
- A test for pre-symptomatic MS could provide windows for early treatment to delay or prevent MS
Immune response to EBV might mistakenly target the brain in MS
MS is an autoimmune disease where the immune system mistakenly attacks the protective “myelin” coating around the nerves in the brain and spinal cord. The loss of myelin interrupts nerve signalling to and from the brain and spinal cord to the rest of the body. Ultimately, this damage causes loss of nerve fibres.
International research suggests Epstein-Barr virus (EBV) might be involved in these processes. EBV is a common virus that causes glandular fever in some people, while in others, it causes no symptoms at all.
EBV infection is likely essential for the development of MS. The body’s immune response to EBV generates antibodies against different parts of the viral proteins to help fight the infection.
In particular, the immune system makes antibodies to an EBV protein called EBNA-1. Parts of EBNA-1 are very similar to proteins in the brain. Antibodies that target EBNA-1 during EBV infection can also recognise these brain proteins, because they are so similar to EBV that the immune system can’t distinguish them. This case of “mistaken identity” might be key to understanding why the immune system targets the brain in MS.
Measuring antibodies to EBV to predict MS risk
A new study by Vietzen and colleagues from the Medical University of Vienna measured the development of antibodies to the EBV protein, EBNA-1, in people prior to the onset of MS. The goal was to determine whether this could help predict who is at risk of developing MS and how the immune response to EBV evolves over time.
What did the researchers do?
The team tested blood samples from 324 people without MS and 324 people with relapsing-remitting MS. They also tested blood samples taken years before MS diagnosis, to pinpoint the first signs of EBV infection and monitor the development of antibodies to EBNA-1 over time. Specifically, they developed a test for antibodies to the section of EBNA-1, called EBNA-1385-452, that can cross-react with four brain proteins. They also tested for markers of nerve damage in the blood, called serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP).
What did the researchers find?
At the time of MS diagnosis, antibodies to the “brain cross-reactive” part of EBNA-1 (EBNA-1385-452) were higher in people with MS than in people without MS.
High levels of these antibodies were found as early as nine months after the first signs of EBV infection. This was up to 12 years prior to diagnosis with MS (median 5.4 years); and 3.7 years before signs of nerve damage were detectable in the blood (median 3.6 years for sNfL, 3.8 years for GFAP).
People who had continuously high levels of these antibodies after EBV infection were likely to develop MS more quickly. Higher levels of antibodies were associated with signs of more severe disease, both on brain imaging and testing markers of nerve damage in the blood.
What does this mean for predicting MS?
Overall, the study found that almost everyone who was repeatedly positive for high-level antibodies within three years of their first EBV infection was subsequently diagnosed with MS in the follow-up.
Everyone who had continuously high-level antibodies after EBV infection developed MS within seven years after infection.
This confirms that antibodies against this specific part of EBNA-1 were an excellent marker for predicting MS diagnosis in this study.
What’s next?
Measuring antibody levels against this specific part of EBV could prove a very useful blood test to help assess a person’s risk of MS.
It will be important for this promising finding to be confirmed independently in other laboratories. It has also not yet been tested as a predictor for primary progressive MS.
In practice, this test could potentially be used in people at higher risk of MS, such as after glandular fever (symptomatic EBV infection). In those with consistently high antibody levels, brain imaging might be warranted.
At present, there is no way to identify people in the earliest stages of MS before symptoms arise, unless they happen to have brain imaging for other reasons.
If this antibody test can successfully help identify people in the very earliest stages of MS, this might provide a window for early treatment to delay or even prevent conversion to clinical MS.
Early detection and intervention is an important focus of a global initiative underway led by MS Australia and MS Canada, and we look forward to significant progress in this area in the years ahead.
