Multiple Sclerosis: New Evidence for the Role of Glandular Fever Virus

An estimated 2.8 million people worldwide multiple sclerosis (MS), an autoimmune disease in which the immune system damages the brain and spinal cord.

Symptoms include fatigue, vision problems, mobility and balance problems, and cognitive impairment. Many people who develop MS experience symptoms and then recover for some time, but over time the disease can progress to permanent disability.

The exact cause of MS is unknown. But for decades, scientists have suggested a link between MS and Epstein-Barr virus (EBV). This is an infection that is acquired during childhood and usually causes no symptoms. However, adolescent infections can cause glandular fever, also called “kissing disease” or infectious mononucleosis (“mono”).

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A 2022 study confirmed that MS patients almost always had a previous EBV infection (usually, infection occurs several years before the onset of MS).

But researchers are still debating exactly how this common virus causes MS in certain people. Our new research provides some clues.

a little background

When your body encounters an infection, it generates an immune response, so you already have some protection against the disease the next time you get infected.

Normally, healthy people produce immune cells called T cells and B cells against a single target, such as some viruses or bacteria, and their job is to fight infections. B cells produce antibodies that bind to and destroy invading viruses and bacteria.

Autoimmune diseases (MS being one) occur when the body’s immune system mistakenly damages itself. This can be caused by a phenomenon called molecular mimicry, which usually occurs when immune cells originally generated to fight infection instead attack similarly shaped proteins in the body. .

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This causes different symptoms and diseases depending on which part of the body the immune system targets. In MS, the brain and spinal cord are affected, causing a variety of neurological symptoms.

Immunity misdirected

To understand in more detail how this process occurs in MS patients, my colleagues and I studied blood samples from over 700 MS patients and a similar number of people without MS (control group). bottom.

We found that antibodies that bind to an EBV-derived protein called EBNA1 are elevated in MS patients. This should come as no surprise. Previous studies have shown that MS patients have elevated antibodies against her EBNA1.

However, their role in disease remains a question mark. In our study, these antibodies produced in response to EBNA1 do not fight EBV infection, but instead are found in regions of the brain that become inflamed in MS, called alpha crystallin B (Cryab). It turns out that similar proteins can be targeted.

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Cryab plays an important role in protecting against the effects of inflammation, so if antibodies mistakenly target this protein, it could 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 control patients. This suggests that this process may be involved in the induction or progression of MS disease in up to a quarter of patients.

While these findings are intriguing, they also show great variability among people with this disease, suggesting that there may be several slightly different pathways for the development of MS. .

Previous studies have shown that the EBNA1 antibody can also bind to other proteins in the body, such as anoctamine-2 and GlialCAM, which are also commonly found in MS patients.

What about T cells?

EBV antibodies are thought to be involved in MS, but they are unlikely to fully explain why some people develop the disease. Researchers believe that T cells, soldiers of the immune system that work in concert with antibodies, may also be involved.

Therefore, we also investigated the role of T cells and found that T cells may cross-react with EBNA1 and Cryab in a similar manner.

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Although our understanding of how the immune response to EBV contributes to MS, we still do not fully understand what is happening in the early stages of the disease and what drives its progression. Not.

We are now expanding our research to understand how T cells fight EBV infection and how these cells damage the central nervous system. It is possible that other proteins may also be targets of the EBV immune response in MS, and our study explores this possibility.

Although available treatments are highly effective in reducing relapse rates, at present there is no treatment that ultimately prevents disease progression. A better understanding of this disease will hopefully pave the way for the development of personalized therapies that could cure MS.

Olivia ThomasPostdoctoral Fellow, Department of Clinical Neuroscience, Karolinska Institute

This article is reprinted from conversation Under Creative Commons License.read Original work.