How Epstein-Barr Virus Triggers Immune Response in Multiple Sclerosis: New Mechanistic Insights
核心洞察
Researchers have uncovered how Epstein-Barr virus (搜索) (EBV) launches CD4+ T cell (搜索)-driven immune responses that lead to inflammation and nervous system damage in multiple sclerosis (搜索).
The study, published in Science Translational Medicine, found that immune T cell activity was twice as high in people with MS compared to healthy controls, with CD4+ T cells driving the response.
Anti-CD20 therapies (搜索) reduced CD4+ T cell (搜索) levels by approximately 2.5 times and lowered EBV levels in saliva, while the MS drug frexalimab blocks CD4+ T-cell activity to reduce inflammation.
In a study published Wednesday in Science Translational Medicine, researchers have illuminated how Epstein-Barr virus (搜索) (EBV) launches the immune responses that drive the inflammation and nervous system damage characteristic of multiple sclerosis (搜索). The findings represent a significant step toward understanding the mechanistic link between a virus carried by roughly 90% of the global population and a debilitating autoimmune disease affecting approximately 2.9 million people worldwide.
"It's very nice now to be able to understand more about the underlying mechanisms of how EBV likely causes MS," said lead author Kjetil Bjornevik, an assistant professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health.
CD4+ T Cells Identified as Key Drivers
The research team, led by Natalia Drosu, a neurology researcher at Massachusetts General Hospital in Boston, set out to investigate which components of the immune system respond to Epstein-Barr virus (搜索) in the context of MS. Their experiments revealed that immune T cell activity was twice as high in people with MS compared with healthy control individuals.
When the researchers selectively depleted various T cell types in study participants, they observed that immune responsiveness to EBV decreased markedly once CD4+ T cells were removed. This finding pinpointed CD4+ T cells as the primary drivers of the aberrant immune response.
"That suggested we should look at this immune response in particular," Drosu explained, noting that the MS drug frexalimab acts specifically on CD4+ T cells, blocking their activity to reduce inflammation and nerve damage.
Anti-CD20 Therapies and Their Mechanism
The study also shed light on how another class of existing MS drugs — anti-CD20 therapies (搜索) — reduces immune responsiveness to EBV, a mechanism that had previously been unclear. Researchers measured CD4+ T cell (搜索) levels in 60 people with MS before and six months after initiating anti-CD20 treatment. They found that CD4+ T cell levels decreased by approximately 2.5 times after the measurement period.
The team validated these results in a second cohort and confirmed that the reduction in T-cell levels persisted for up to one year. Additionally, individuals receiving anti-CD20 treatment had lower levels of Epstein-Barr virus (搜索) in their saliva compared with both healthy people and those with untreated MS.
Toward Vaccines and Targeted Therapies
The findings carry important implications for future therapeutic development. Researchers hope the mechanistic insights will aid in creating EBV vaccines or antiviral medications capable of preventing or managing MS symptoms while avoiding the major side effects associated with commonly used immunosuppressants.
Syed Rizvi, director of the Multiple Sclerosis (搜索) Center of Rhode Island, who was not involved in the study, emphasized the translational significance. "When you're developing drugs, targeted drugs, every little step, every little molecule, every little antigen is a game changer," he said.
Emily Edwards, a rare-diseases researcher at Monash University in Melbourne, Australia, noted that the results signal that scientists are "starting to get to the bottom of how Epstein–Barr virus drives the development of multiple sclerosis (搜索)."
While EBV is present in about 90% of the global population and remains relatively harmless for most, it is now "well established" that the virus is one of the main causes of MS for a subset of individuals, according to Drosu. In MS, immune cells attack the protective myelin sheath surrounding nerves, leading to vision problems, difficulty walking, and other neurological symptoms. Current treatments can slow disease progression and reduce the frequency and severity of symptom episodes, but no cure exists.