More Evidence for Epstein - Barr virus' Role in MS Found

The Epstein-Barr virus (EBV) is a common virus that causes glandular fever (infectious mononucleosis), usually in teenagers and young adults. It has been proposed as a possible trigger for multiple sclerosis, and is also implicated in some cancers.

A number of other viruses have been investigated, including chicken pox, measles, mumps, canine distemper and a number of herpes viruses. However, if there is a particular virus or combination of viruses that trigger multiple sclerosis (MS), the exact mechanism still has to be identified.

Image: Infections by Epstein-Barr virus usually cause no symptoms, but a growing body of evidence suggests it plays a role in multiple sclerosis (Photo courtesy of Kateryna Kon, MD, PhD)

Medical Scientists at the University of Münster (Münster, Germany) sequenced the T-cell receptor variable beta-chain (TRBV) peripheral repertoire among three cohorts of MS patients: A discovery cohort with 1,336 patients with MS and 229 controls; a validation cohort with 59 patients with MS and 51 controls; and 35 monozygotic twins who were discordant for MS.

The investigators identified sequences known to bind to EBV, SARS-CoV-2, cytomegalovirus, and influenza A, and used the latter three viruses as a proof of concept to demonstrate the validity of the approach. EBV-specific MHC-1 restricted CD8 TRBV in the serum of MS patients, with large effect sizes in the discovery (+2.2), validation (+2.1), and MS twin (+1.6) populations. The findings in the twin population rule out a genetic or environmental explanation for the findings in the discovery and validation cohorts. They also sequenced CSF among six healthy donors and five patients with MS and found significant differences. The T-cell populations had more lytic properties that suggested ongoing immune surveillance.

Tilman Schneider-Hohendorf, PhD, a post-doctoral fellow and lead author of the study, said, “We can conclude that we found a broader response that could indicate an aberrant immune response. This could be a remnant of disease triggering an event or it could indicate an ongoing immune response to EBV. Is this EBV activity? We really don't know. To find out, we would expand our pathogen-specific sequences, we would assess CNS tissue and lesions, and we would define the primary response in pediatric cohorts to better understand what might go wrong.”

The study was presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis held October 26 to 28, 2022 in Amsterdam, Netherlands.

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