New Insights into Epstein-Barr Virus and Multiple Sclerosis

For years, a common virus has been linked to the onset of multiple sclerosis (MS), a condition that triggers the immune system to attack nerve cells in the brain and spinal cord. Recently, researchers revealed how this virus activates the immune response. They also disclosed that a particular immunotherapy could help prevent relapses and slow the disease’s progression. These findings were published in Science Translational Medicine.

Researchers are gradually uncovering how Epstein–Barr virus contributes to multiple sclerosis, remarks Emily Edwards, a researcher focusing on rare diseases at Monash University in Melbourne, Australia.

This herpesvirus is found in nearly 90% of people globally, and for most, it’s typically benign. However, a certain subset has a well-established connection between Epstein–Barr virus and MS, according to study co-author Natalia Drosu, a neurology researcher at Massachusetts General Hospital in Boston. Yet, the mechanism behind this connection remained unclear until now.

In the context of MS, immune cells target the myelin sheath around nerves, causing symptoms like vision problems and mobility issues. The condition affects around 2.9 million people worldwide. While current treatments can slow progression and alleviate symptoms, there’s still no cure.

Investigating Immune Response

Drosu and her team aimed to pinpoint how the immune system reacts to Epstein–Barr virus. They discovered that T cell activity was significantly elevated—twice as high—in individuals with MS compared to healthy controls. When they selectively depleted certain T cell types, they noticed a remarkable drop in immune responses when they eliminated CD4⁺ T cells, indicating their crucial role.

One reason they focused on CD4⁺ T cells was due to a drug for MS, frexalimab, which targets these cells to reduce inflammation and nerve damage by blocking their activity. “This led us to specifically examine this immune response,” Drosu explains. The study also mentions another group of therapies known as anti-CD20, which dampened immune response to the virus but lacked clarity on their mechanism.

To explore this further, the researchers analyzed CD4⁺ T cell levels in 60 MS patients before and six months after starting anti-CD20 treatment. They found that these levels had decreased roughly 2.5 times after treatment. Validation with a second cohort confirmed that this reduction could last for up to a year.

Additionally, participants undergoing anti-CD20 therapy exhibited lower Epstein-Barr virus levels in their saliva when compared to healthy individuals and those not receiving treatment.

Edwards points out that this suggests treatment could curb viral activity. Anti-CD20 therapy works by targeting and eliminating a different immune cell type, B cells, which are infected. With fewer B cells present, there’s less stimulus for CD4⁺ T cells to react, which results in a more subdued immune response. “This underscores the roles of both immune cell types in driving disease and highlights how we can potentially mitigate disease severity with immunotherapies,” Edwards adds.