ACTRIMS 2026: New study questions whether EBV precedes every MS case
Researchers found MS-related claims before first positive EBV test
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- A study questions whether Epstein-Barr virus (EBV) infection is required for every case of multiple sclerosis (MS).
- Some patients had MS-related claims before their first positive EBV test.
- Researchers say it is too soon to rule out MS based solely on a negative EBV antibody test.
A Canadian study is challenging the growing belief that previous infection with the Epstein-Barr virus (EBV) is necessary for multiple sclerosis (MS) to develop. The findings suggest the virus may not precede every MS case.
Using public health insurance claims data, the researchers found a small group of people whose MS-related diagnostic claims appeared before their first positive test suggesting primary EBV infection.
Presentation raises questions about EBV timing
Dalia Rotstein, MD, of the University of Toronto, discussed the findings and their implications in an oral presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026, held last week in San Diego and virtually. The work was funded by MS Canada and the National MS Society.
“I think our findings raise the question of whether EBV infection is required in all cases for the development of MS,” Rotstein said in the presentation titled, “Is it possible for MS onset to precede EBV infection? A population-based assessment.”
EBV is a common virus that infects more than 90% of people at some point in their lives, usually during childhood. Because it typically causes mild or no symptoms, most people do not realize they were infected.
Over the years, research has positioned a history of EBV infection as a leading risk factor for MS. Some researchers have proposed that infection may be necessary for the disease to develop. In light of that, some clinicians are using a negative EBV test to rule out an MS diagnosis, according to Rotstein.
However, Rotstein cautioned that those who do so may be falling into the so-called “post-hoc logical fallacy.” In other words, just because virtually all people who develop MS have been infected with EBV, it doesn’t necessarily mean the virus is the single definitive cause of the neurodegenerative disease.
To establish that, it must also be true that people who haven’t been exposed to EBV will not develop MS.
“We actually have very few studies exploring EBV seronegative cases,” Rotstein said. In this context, seronegative refers to people without a documented positive EBV antibody test.
Large database study explores EBV test sequence
To find whether there are people in the general population who might be diagnosed with MS before testing positive for anti-EBV antibodies, the scientists analyzed health claims data from Ontario, Canada. This allowed them to examine a large, ethnically diverse group of people with free access to healthcare services.
From these records, the team identified nearly 96,000 people who tested positive for antibodies indicating a primary EBV infection.
Within this group, 74 people had diagnostic codes in their records suggesting MS-related claims appeared before their first positive EBV test. The group had characteristics similar to those of the general MS population.
I think our findings raise the question of whether EBV infection is required in all cases for the development of MS.
Rotstein said there are several possible explanations for these findings, including that some people may have been misdiagnosed with MS. It is also possible the EBV test results were inaccurate, or that what appeared to be an initial EBV infection was actually a later reactivation of the virus.
A key limitation of this study is that there were no EBV antibody measurements available before these patients’ MS diagnoses, making it impossible to confirm their EBV status at the time.
“But given the number of cases, I think we need to entertain the probability of a fourth hypothesis,” the scientist said.
Researchers caution against firm conclusions
Rotstein said the data raise the possibility that EBV may not be a universal driver of MS, and that other factors could contribute to the same symptoms. For example, some research has suggested that other viruses, such as human herpesvirus 6A, may also play a role in MS development.
She pointed to a related condition, neuromyelitis optica spectrum disorder. Although it is usually linked to a specific type of self-reactive antibody, there are antibody-negative cases with the same clinical profile.
Based on the data, she said it’s too soon to conclude that a negative EBV antibody test can rule out an MS diagnosis.
Rotstein emphasized that the findings are not meant to undermine the strong evidence linking EBV and MS but instead highlight the need to better understand the small proportion of cases in which the timing does not follow the expected pattern.
“Enhancing our understanding of EBV seronegative cases will only help us as we move forward with preventative and therapeutic approaches targeting EBV,” the scientist concluded.
The Multiple Sclerosis News Today team is providing virtual coverage of the ACTRIMS Forum 2026 from Feb. 5-7. Go here to see the latest stories from the conference.
