Approximately 2.8 million people in the world have multiple sclerosis (MS), an autoimmune disease in which the immune system damages the brain and spinal cord.
Symptoms include fatigue, blurred vision, mobility and balance problems, and cognitive dysfunction. Many people who develop MS experience symptoms followed by a period of recovery, but over time the disease can progress to permanent disability.
The exact causes of MS are unknown. But for decades, scientists have suggested a link between MS and Epstein-Barr virus (EBV). This is an infection that, when contracted in childhood, usually does not cause symptoms. However, infection in adolescence can lead to glandular damage. feveralso called “kissing disease” or infectious mononucleosis (“mono”).
A study 2022 confirmed that people with MS have almost always been infected with EBV before (usually the infection occurs several years before the onset of MS).
But researchers are still debating exactly how this joint virus may cause MS in some people. OUR new search offers some clues.
A bit of context
When your body encounters an infection, it generates an immune response so that the next time you are exposed, you will already have some protection against the disease.
Normally, in healthy people, immune cells called T cells and B cells are generated against a single target, such as part of a virus or bacteria, and their job is to fight infection. B cells produce antibodies that bind and destroy the invaders virus or bacteria.
Autoimmune diseases – of which MS is one – occur when the body’s immune system mistakenly damages itself. This may be caused by a phenomenon called molecular mimicrywhich usually happens when immune cells, originally generated to fight infection, instead attack similarly shaped proteins in the body.
This causes a variety of symptoms and illnesses depending on which part of the body the immune system is targeting. In MS, because the brain and spinal cord are affected, the disease causes a range of neurological symptoms.
Misdirected immunity
To understand in more detail how this process takes place in MS patients, my colleagues and I studied blood samples from more than 700 people with MS and a similar number without the disease (a control group).
We found that antibody that bind to an EBV protein, called EBNA1, were increased in MS patients.
This was not surprising – previous research showed antibodies against EBNA1 are higher in people with MS. But their role in the disease remained a question mark.
Our study found that these antibodies generated in response to EBNA1, rather than fighting EBV infection, may instead target a similar-looking protein found in areas of the brain that become inflamed in MS, called alpha-crystallin B, or Cryab.
Cryab plays a crucial role in protecting against the effects of inflammation, and so if antibodies mistakenly target this protein, it could partly explain the symptoms seen in MS.
We found that these Cryab antibodies were present in up to 23% of MS patients and only 7% of controls, suggesting that this process may be involved in the initiation or progression of MS in up to one quarter of patients.
These results are intriguing, but show that there is great variation between people with the disease and suggest that there may be several slightly different ways MS develops.
Previous studies have shown that EBNA1 antibodies can also bind to other proteins in the body such as anoctamine-2 And GlialCAMalso more common in people with MS.
What about T cells?
Although EBV antibodies are thought to be involved in MS, they are unlikely to fully explain why some people develop the disease. Researchers believe T cells – immune system soldiers who work alongside antibodies – could also be involved.
So we also investigated the role of T cells and found that they can probably cross-react with EBNA1 and Cryab in the same way.
Despite these advances in our understanding of how the immune response to EBV may be involved in MS, we still do not fully understand what happens early in the disease or what drives its progression.
We are now expanding our research to understand how T cells fight EBV infection and how these cells can damage the central nervous system.
It is likely that other proteins may also be targeted by EBV immune responses in MS, and our research is exploring this possibility.
Although available therapies are very effective in reducing relapse ratethere is currently no treatment that ultimately prevents the progression of the disease.
Hopefully, a better understanding of the disease will pave the way for the development of personalized therapies that can cure MS.
Oliver ThomasPostdoctoral Researcher, Department of Clinical Neurosciences, Karolinska Institute
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