Friday, June 2, 2023

Common viral antibodies could trigger MS, research reveals

Scientists have uncovered how a common childhood virus could trigger multiple sclerosis (MS), in findings that could pave the way for new treatments for the devastating condition.

The research suggests that the body’s immune response to the Epstein-Barr virus (EBV), a normally harmless infection, can misfire and mistakenly target a crucial protein in the brain and spinal cord.

“MS is an incredibly complex disease, but our study provides an important piece in the puzzle and could explain why some people develop the disease,” said Dr Olivia Thomas, of Sweden’s Karolinska Institute and shared first author of the paper.

“We have discovered that certain antibodies against the Epstein-Barr virus which would normally fight the infection can mistakenly target the brain and spinal cord and cause damage.”

The discovery could help the development of treatments to protect the central nervous system from being damaged by the immune system. Current therapies are effective at reducing relapses in MS but none can prevent disease progression.

The advance follows a landmark 20-year study of 10 million US military personnel published last year, which provided compelling evidence that Epstein-Barr can trigger MS. It showed that those infected with EBV are 32 times more likely to develop the incurable condition.

“We know it’s almost a prerequisite to developing MS – you can’t really get MS without getting EBV first,” said Thomas. “Epidemiologically we’re pretty convinced that EBV is one of the main factors, but we’re still not sure what the mechanism is.”

EBV is one of the most widespread viruses in humans. More than 90% of the world’s population are infected and most people only experience mild cold symptoms. After infection, the virus sits dormant in the body, kept suppressed by antibodies.

However, the latest work suggests that, in some people, these antibodies could be involved in triggering MS.

They found that antibodies that bind to a certain protein in the Epstein-Barr virus, EBNA1, can also bind to a very similar-looking protein in the brain and spinal cord called CRYAB, which plays a crucial role in protecting against the effects of inflammation.

If antibodies are mopping up CRYAB, this could result in damage to the nervous system and contribute to severe symptoms in MS patients, including problems with balance, mobility and fatigue.

The researchers analysed blood samples from more than 700 patients with MS and 700 healthy individuals and found the cross-reactive antibodies were present in about 23% of MS patients and 7% of control individuals.

“This shows that, whilst these antibody responses are not required for disease development, they may be involved in disease in up to a quarter of MS patients,” said Thomas. “This also demonstrates the high variation between patients, highlighting the need for personalised therapies.”

The scientists believe that T-cells, which work in parallel with antibodies, could target the same EBV protein, meaning that they are also likely to be involved in generating an autoimmune response. This could at least partly account for how the virus triggers MS in patients who tested negative for the antibodies.

It is also not clear why some healthy people carry the antibodies without apparently any detrimental effect. One possibility is that, in these people the antibodies were only present in blood, but in the MS patients they had crossed the blood-brain barrier.

The findings are published in the journal Science Advances.

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