Study finds EBV may be leading environmental cause of MS

Published: 19 October 2022

A new Spanish study has found people with multiple sclerosis (MS) are much more likely to have Epstein-Bar virus (EBV) antibodies than healthy individuals.

EBV causes glandular fever and is very common among the general population. Previous studies have found that MS rarely, if ever, happens in a person who has never been infected with EBV, and the virus is thought to be the strongest risk factor for the disease.

In this study, 325 MS patients, and 295 healthy people, who were blood donors and served as a control group, were included.

The MS patients were being treated with disease-modifying therapies (DMTs) interferon-beta drugs or Tysabri for two years. Samples of their blood were collected before starting treatment and two years after and analysed for EBV antibodies – EBNA-1 which identifies an older infection, and VCA which generally signals a more recent infection.

When tested before the DMTs, all of the MS patients were positive for at least one of the antibodies, compared with 94.9% of those without MS – a statistically significant difference. The blood levels of the MS group’s antibodies were also significantly higher.

Researchers said that this confirms that MS ‘occurs rarely in the absence of EBV as it has been previously suggested.’

The team also found that a particular form of the gene HLA-DRB1*15:01 – which is not only a predisposing factor for MS but is also linked to EBV antibody levels – called DR3, was associated with lower anti-EBNA-1 antibody levels, whereas the DR6 form was linked to higher levels. These genes give instructions for the body to make proteins that play a critical role in immune system activation.

MS patients with the rs11129295TT variant in the EOMES gene had significantly higher anti-EBNA-1 antibody levels. The EOMES gene produces codes for a protein whose immune function appears to be reduced in MS patients.

The researchers found what they called ‘an intriguing association’ when they found participants with the gene variants that were associated with lower EBNA-1 antibody levels tended to develop MS an average of 3.5 years later than people without them. These antibody levels were also found to be significantly higher in MS patients who had fewer relapses in the two years before they went onto DMTs, and anti-VCA antibody levels increased with age.

The researchers wrote that while the “DMTs included in this study did not change significantly the [levels] of the anti-EBV antibodies analysed, similar studies with B-cell depleting MS therapies are needed.”