Multiple Sclerosis and Epstein-Barr virus infection

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SUMMARY

The discussion centers on the significant correlation between Epstein-Barr virus (EBV) infection and the increased risk of developing Multiple Sclerosis (MS), with a 32-fold increase in risk identified through a longitudinal study involving over 10 million US military personnel. The research highlights that EBV infection often precedes MS diagnosis by several years and suggests that an EBV vaccine could substantially reduce MS incidence. However, the development of such a vaccine faces challenges, including ethical concerns in human testing and the need for a comprehensive understanding of the economic impact of infectious mononucleosis.

PREREQUISITES
  • Understanding of Epstein-Barr virus (EBV) and its implications in human health.
  • Familiarity with Multiple Sclerosis (MS) as a chronic inflammatory disease.
  • Knowledge of serological testing and biomarkers like neurofilament light chain.
  • Awareness of vaccine development challenges and ethical considerations in clinical trials.
NEXT STEPS
  • Research the latest advancements in EBV vaccine development and trials.
  • Explore the role of neurofilament light chain as a biomarker in MS diagnosis.
  • Investigate the societal and economic impacts of infectious mononucleosis.
  • Study the relationship between EBV reactivation and long COVID symptoms.
USEFUL FOR

This discussion is beneficial for medical researchers, immunologists, neurologists, and public health professionals interested in the links between viral infections and autoimmune diseases, as well as those involved in vaccine development and ethical considerations in clinical research.

jim mcnamara
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TL;DR
Infection of brain tissue by the Epstein-Barr virus is found to precede the diagnosis of Multiple Sclerosis.
Statnews article:
https://www.statnews.com/2022/01/13/strong-new-evidence-suggests-virus-triggers-multiple-sclerosis/

Evidence from a colossal blood bank at Walter Reed Army Hospital allowed researchers to look over a long time span of samples for a huge number of US service men/women. The blood bank had multiple samples over time for every service man/woman starting when the person entered the military, usually in their late teens. Epstein-Barr infection was found to increase the subsequent rate of MS by a factor of 32. It often precedes the MS diagnosis by several years.

The article discusses changes in brain tissue that can be found in blood samples, and what changes occur with MS and show up in blood samples. They suggest that a vaccine against EBV would greatly reduce the incidence of MS.
 
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Wow, that's good news. Do we have a vaccine yet for EBV?
 
berkeman said:
Do we have a vaccine yet for EBV?
Hmm, looks like that is work in progress...?

https://www.frontiersin.org/articles/10.3389/fimmu.2021.677027/full

1642124260195.png
 
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Here is one answer about why EBV vaccines are not simple.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636506/
Example claim: human testing could involve increased risk of carcinogenesis and other pathologies under several different scenarios that have come to the fore in development.

In other words testing on human subjects has potential to violate all kinds of ethical boundaries. Kill 'em or cure 'em is not a cool approach.
 
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jim mcnamara said:
Here is one answer about why EBV vaccines are not simple.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636506/

The review article lists "the need for additional information on the economic and societal burden of infectious mononucleosis to assess the cost-benefit of a prophylactic vaccine" as an important barrier to the development of an EBV vaccine. Hopefully the connection between EBV infection and MS helps to address this barrier.
 
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Here's a link to the paper reporting the discovery, published in the journal Science:

Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis
https://www.science.org/doi/10.1126/science.abj8222

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.

Here's one of the key figures from the paper, comparing the prevalence of infection with EBV or cytomegalovirus (CMV, a similar virus used as a control) in patients who later developed MS vs not:
1642206400684.png


The data do make a clear case that EBV infection greatly increases the risk of developing MS, but there are also plenty of people who get infected by EBV but do not go on to develop MS (e.g. ~60% of the MS negative group showed signs of EBV infection in their third sample). So, EBV infection seems likely to be necessary but not sufficient for MS. It will be important to discover the factors that differentiate whether an EBV infection leads to MS in some individuals but not in others. (Perhaps this research could also shed light on the similar problem of why SARS-CoV-2 infection leads to long COVID is some individuals but not others).
 
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Pardon the anecdotes but note that infectious 'mono' caused by EBV ravaged my age cohort circa 1960's.

I remember sleeping at home for weeks with a persistent sore throat, nursed by my older sister who later became an RN based partially on attending me and dozens of school friends. A close friend from across the country claimed they 'lost nearly a year of childhood due to mono'. The outbreak at my school was traced to water fountains where low water pressure often required mouth contact.

The virus seemed to return with symptoms of sleepiness, tiredness and persistent sore throat concomitant with bouts of flu into early adulthood. While measles infection caused more pain and some minor scars, childhood EBV affected our lives and educations for a much longer period. I understand an effective measles vaccine now exists.

The crux of these anecdotes is that a vaccine for EBV has merit notwithstanding the probable connection to developing multiple sclerosis.
 
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See also:

Sagittarius A-Star said:
I found something interesting about long covid:

Long COVID and severe COVID-19 infections associated with Epstein-Barr virus reactivation
...
"We ran Epstein-Barr virus serological tests on COVID-19 patients at least 90 days after testing positive for SARS-CoV-2 infection, comparing EBV reactivation rates of those with long COVID symptoms to those who never experienced long COVID symptoms," said lead study author Jeffrey E. Gold of World Organization. "We found over 73% of COVID-19 patients who were experiencing long Covid symptoms were also positive for EBV reactivation."
...
"If a direct role for EBV reactivation in long COVID is supported by further studies, this would provide opportunities to improve the rational diagnosis of this condition and to consider the therapeutic value of anti-herpesvirus agents such as ganciclovir."

Source:
https://www.eurekalert.org/news-releases/612727
 
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