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Epstein-Barr virus may be leading cause of Multiple Sclerosis – Harvard cohort study

Multiple Sclerosis (MS), a progressive disease that affects 2.8m people worldwide and for which there is no definitive cure, may be caused by infection with the Epstein-Barr virus (EBV), according to a study led by Harvard TH Chan School of Public Health researchers and published online in Science.

“The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality,” said Alberto Ascherio, professor of epidemiology and nutrition at Harvard Chan School and senior author of the study.

“This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.”

MS is a chronic inflammatory disease of the central nervous system that attacks the myelin sheaths protecting neurons in the brain and spinal cord. Its cause is not known, yet one of the top suspects is EBV, a herpes virus that can cause infectious mononucleosis and establishes a latent, lifelong infection of the host.

Establishing a causal relationship between the virus and the disease has been difficult because EBV infects approximately 95% of adults, MS is a relatively rare disease, and the onset of MS symptoms begins about 10 years after EBV infection.

To determine the connection between EBV and MS, the researchers conducted a study among more than 10m young adults on active duty in the US Military and identified 955 who were diagnosed with MS during their period of service.

The team analysed serum samples taken biennially by the military and determined the soldiers’ EBV status at time of first sample and the relationship between EBV infection and MS onset during the period of active duty.

In this cohort, the risk of MS increased 32-fold after infection with EBV but was unchanged after infection with other viruses. Serum levels of neurofilament light chain, a biomarker of the nerve degeneration typical in MS, increased only after EBV infection.

The findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

Ascherio says that the delay between EBV infection and the onset of MS may be partially due the disease’s symptoms being undetected during the earliest stages and partially due to the evolving relationship between EBV and the host’s immune system, which is repeatedly stimulated whenever latent virus reactivates.

“Currently there is no way to effectively prevent or treat EBV infection, but an EBV vaccine or targeting the virus with EBV-specific antiviral drugs could ultimately prevent or cure MS,” he said.

Study details

Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

Kjetil Bjornevik, Marianna Cortese, Brian Healy, Jens Kuhle, Michael Mina, Yumei Leng, Stephen Elledge, David Niebuhr, Ann Scher, Kassandra Munger, Alberto Ascherio.

Published in Science on 13 January 2022.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service.
Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion.
These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.

 

Science abstract – Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis (Open access)

 

See more from MedicalBrief archives:

 

Misdiagnosis of multiple sclerosis found to be common

 

Early treatment of MS symptoms delays progression to disability

 

Clinical trial finds MS drug slows brain atrophy

 

 

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