A new study suggests the role Epstein-Barr virus plays in multiple sclerosis development may be caused by a higher level of cross-reactivity – where the body’s immune system binds to the wrong target – than previously thought.

University of Birmingham researchers looked at blood samples from people with MS, as well as healthy people infected with EBV, and people recovering from glandular fever caused by recent EBV infection. The study investigated how the immune system deals with EBV infection as part of worldwide efforts to understand how this common virus can lead to the development of MS, following 20 years of mounting evidence showing a link between the two.

While previous studies have shown that antibody responses to one EBV protein – EBNA1 – also recognize a small number of proteins of the central nervous system, this study found that T-cells, another important part of the immune system, that target viral proteins can also recognize brain proteins.

A second important finding was that these cross-reactive T-cells can be found in people with MS but also in those without the disease. This suggests that differences in how these immune cells function may explain why some people get MS after EBV infection.

The study’s authors said their findings have two main implications. First, the findings give greater weight to the idea that the link between EBV and MS is not due to uncontrolled virus infection in the body. Second, they have shown the human immune system cross-recognizes a much broader array of EBV and central nervous system proteins than previously thought, and that different patterns of cross-reactivity exist. Knowing this will help identify which proteins are important in MS and may provide targets for future personalized therapies.

During testing of blood, the team also found evidence that cross-reactive T cells that target Epstein-Barr virus and central nervous system proteins are also present in many healthy individuals. The researchers said the detection of cross-reactive T-cells in healthy individuals suggests that it may be the ability of these cells to access the brain that is important in MS.

The study was published in the journal PLOS Pathogens.