For years, a common virus has been implicated in the development of multiple sclerosis, a disease in which the body’s immune system attacks nerve cells in the brain and spinal cord. Now, researchers have discovered how the virus activates the immune system. They also reveal how an immunotherapy treatment can prevent relapses and slow the progression of the disease.¹. The results are published today in Science translational medicine.

The findings are a sign that scientists are starting to get to the bottom of how the Epstein-Barr virus drives the development of multiple sclerosis (MS), says Emily Edwards, a rare disease researcher at Monash University in Melbourne, Australia.

The Epstein-Barr virus is a herpesvirus present in approximately 90% of the world’s population. For most people, the infection is relatively harmless and does not cause MS. But for a subset of the population, it is “well established” that the Epstein-Barr virus is a leading cause of MS, according to study co-author Natalia Drosu, a neurology researcher at Massachusetts General Hospital in Boston. But until now it was unknown how the virus triggers the disease.

In MS, immune cells attack the protective myelin sheath that surrounds the nerves, causing vision problems and difficulty walking. It affects around 2.9 million people worldwide. Currently, people with MS can take medications to slow the progression of the disease and reduce the frequency and severity of episodes in which symptoms worsen, but there is no cure.

Immune system response

Drosu says she and her team wanted to investigate which parts of the immune system respond to the Epstein-Barr virus. They showed that immune T cell activity was twice as high in people with MS compared to healthy controls. When the researchers selectively reduced the levels of several types of T cells in the participants, they found that people’s immune responsiveness to the virus decreased markedly once a specific type known as CD4 was detected.⁺ T cells were eliminated, indicating that this group drives the response.

Drosu says another reason they focused on CD4⁺ The T cells were because a drug used to treat MS, called frexalimab, acts on them. The treatment reduces inflammation and nerve damage by blocking CD4.⁺ T cell activity. “That suggested we should look at this particular immune response,” he explains. Another class of existing drugs called anti-CD20 therapies also reduce the immune system’s responsiveness to Epstein-Barr virus, but it was unclear how, the study notes.

To find out, the researchers measured CD4 levels⁺ T cells in the bodies of 60 people with MS before and six months after starting anti-CD20 treatment. They found that CD4 levels⁺ T cells in the participants’ bodies decreased about 2.5 times after the measurement period. The team validated their results in a second group of people and found that the reduction in T cell levels persisted for up to a year.

Another group of people who received anti-CD20 treatment also had lower levels of Epstein-Barr virus in their saliva compared to healthy people and people with untreated MS.

Edwards says this suggests that the treatment reduces the amount of viral activity in the body. Anti-CD20 therapy works by binding to and destroying another type of immune cell, called B cells, that are infected. Because there are fewer B cells, CD4⁺ T cells have fewer stimuli to respond to, leading to a reduced immune response. “This shows the importance of both groups of immune cells in causing disease and how we can moderate them with immunotherapies to potentially reduce the severity of the disease,” Edwards adds.