Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis, Bjornevik et al (2022)

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"Study identifies how Epstein-Barr virus triggers multiple sclerosis
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A new study found that part of the Epstein-Barr virus mimics a protein made in the brain and spinal cord, leading the immune system to mistakenly attack the body’s nerve cells.---"

I recall th molecular mimicry discussions on this forum - so this caught my attention!

https://med.stanford.edu/news/all-news/2022/01/epstein-barr-virus-multiple-sclerosis.html

https://www.nature.com/articles/s41586-022-04432-7

 

FYI the Guardian has a long piece today on the paper published in Science:

Can we vaccinate against Epstein-Barr, the virus you didn’t know you had? | Science | The Guardian

I don't suppose, when the team from Harvard TH Chan School of Public Health did their big longitudinal study (10m blood samples from US military personnel over 20 years), they looked at incidence of ME/CFS as well?

 

Interesting i.e. "I don't suppose, when the team from Harvard TH Chan School of Public Health did their big longitudinal study (10m blood samples from US military personnel over 20 years), they looked at incidence of ME/CFS as well?"
If you search on this thread then I think you'll find a comment from Jonathan indicating that that is a reasonable idea [EDIT - see below*]. I might drop Solve an email i.e. to ask if anyone is doing that/thinking of doing that.

[EDIT - I've consulted internally and the thinking is to leave it for a short period of time - so possibly I'll email Solve in a few weeks.
If you want to press ahead then try Emily Taylor (Vice President of Advocacy and Engagement) and Oved Amitay (President and Chief Executive Officer) - Solve.
If you contact them then grateful if you tag me here.]

@Michiel Tack

*
https://www.s4me.info/threads/longi...bjornevik-et-al-2022.24194/page-2#post-401820

 

The quest to prevent MS — and understand other post-viral diseases. Nature news. 3/30/22

https://www.nature.com/articles/d41...ail&utm_term=0_c9dfd39373-3b524abd63-45313962

 

Merged thread

The quest to prevent MS — and understand other post-viral diseases

Erin Longbrake, a neurologist at Yale University in New Haven, Connecticut, has thought about how to balance the need for early intervention with the side effects a treatment can bring. Her therapy of choice is the FDA-approved MS drug ocrelizumab, which kills B cells to reset the malfunctioning immune system. It was not designed as an antiviral, but by happy accident it knocks out at least some of the EBV reservoir. Because it broadly depletes the immune system, however, treated individuals are at high risk of other infections. It’s a high price to pay for someone without a disease.

So Longbrake has been looking for those with most to gain. A tiny subset of people have damaged areas in their brains similar to those caused by MS, but none of the accompanying symptoms. Such lesions are sometimes noticed incidentally on a brain scan. Nearly half of these people will develop MS within ten years of the discovery.

https://www.nature.com/articles/d41586-022-00808-x

 

Ocrelizumab is essentially the same as rituximab. Its effect on MS probably has nothing to do with depleting EBV though, even if EBV is a necessary factor in genesis of the problem. The drugs remove the B cells that give rise to antibody-secreting plasma cells in brain.

The problem about using Rituximabb or ocrelizumab early is that as far as we know from the dozen or so diseases that have been treated since we started with RA you do not get any special bonus from early intervention. You do not get rid of the problem long term, but have to repeat treatment at intervals. This is not always so. Immune thrombocytopenia may remit permanently but it does that anyway so is a bit unusual.

So treating early is a good idea for MS to prevent attacks but I don't see any special relevance to the potential role of EBV.

The risk from infection is not that great - unless you have a pandemic going on, which has proved a major issue. The bigger risk is from pneumonitis, which has never been properly studied so that it can be avoided if possible. It is a sad fact that since we introduced rituximab in 2000 not very much progress has been made in streamlining the treatment and reducing risk, other than patenting new versions that may be a bit more potent, like ocrelizumab.

 

The B cells are EBV infected, that is why Rituximab probably works.

 

I think that is very unlikely. The presence of EBV in our B cells generally has no consequences. It just sits there. If it proliferates the B cell is killed. In all autoimmune diseases something else has happened to the B cell population that is not removed simply by temporary removal of EBV infected cells. The response kinetics in MS with rituximab and ocrelizumab is of blockage of new relapses during the period off B cell depletion but not long term. The role of EBV in MS is almost certainly as an early permissive step. Remember, I introduced rituximab for autoimmune disease in 1998 and before that my mother was in charge of the central EBV virology lab in the UK! I recommended rituximab for blocking MS attacks to the neurologists in 2002 but it took them ten years to get around to it. The rationale was independent of EBV. The kinetics of these diseases are complicated.

 

I think ATA 188 is/will be showing that you are wrong.

 

Can you give a reason for saying this?

As far as I can see ATA 188 kills B cells, so if it works either explanation would fit.
It doesn't look as if there are any firm data yet.
The blurb looks fairly simplistic immunology to me. That does not mean that the drug will not work but I don't see any reason to follow the theorising which is very vague and hand-waving.

I see that there is a possibility that this approach might remove dormant EBV long term and that might lead to long term remission in MS, but that is not what happens with rituximab, which has no specificity for EBV infected cells and does not produce long term remission.

 

No, it kills infected B cells. Big difference.

 

Yes, I guess that if ATA 188 worked it would suggest that MS lesions are specifically mediated by EBV infected cells. But it would be a pretty big coincidence that rituximab works comparably well for all sorts of autoimmune disorders where there is no particular suggestion that EBV infection of the relevant B cells is necessary. Other autoimmune disorders have been documented in EBV negative individuals.

 

https://www.bbc.co.uk/news/health-61042598

 

Why do people get long COVID? A virus called EBV, which causes multiple sclerosis, may hold clues
Scientists are looking at reactivation of latent viruses, and other existing post-infection syndromes, for answers about long-haul COVID-19.

https://eu.azcentral.com/in-depth/n...xamining-long-covid-other-viruses/6900178001/

 

Solve M.E. CEO Oved Amitay and Dr. Leonard Jason Write Letter to the Editor, Nature

"DePaul Univeristy Professor of Psychology Leonard Jason, PhD and Solve M.E. President and CEO Oved Amitay recently co-authored a response to a Nature article linking Epstein-Barr virus (EBV) and multiple sclerosis (MS), and the possibility that EBV vaccines and antivirals could prevent MS. Jason and Amitay note the connection between ME/CFS and EBV call for similar research into preventive vaccines for ME/CFS."

https://solvecfs.org/solve-m-e-ceo-...nard-jason-write-letter-to-the-editor-nature/

 

Bizarre attempt to push the psychosocial (labeled biosocial in the article, for some reason) model that stress is the explanation they prefer. Following the exact same pattern as happened with peptic ulcers, ideology just never gives up.

Falling down the biological rabbit hole: Epstein-Barr virus, biography, and multiple sclerosis
https://www.jci.org/articles/view/164141

It's basically the exact same tired BPS nonsense. Although I guess this is the latest rebranding attempt, biopsychosocial is dead, all hail biosocial, somehow still 99% psychological despite having dropped the prefix.

The main argument appears to be that the cohort in which it was observed was active duty, which would actually strongly support the hypothesis that exertion could be a significant trigger. Not many occasions to rest while on active military duty.

A side note, I read a lot of military sci-fi, often written by veterans. All the good ones are. Military life is not stressful, it's boring. Boring, boring, boring. So much waiting, so much bureaucracy, so much paperwork. Did I mention all the waiting around being bored? What a lot of people love about the military is that it's not complicated, you follow orders, you're told how and where to live.

And most active duty personnel see little combat. Long gone are the days of WWI military type of infernal trench warfare. Especially in the US, active duty soldiers keep in touch with their families, they feel like they belong.

For some reason the message is that biology is not that relevant, while psychology is, but they want to call it biosocial. Whatever. What a mess this ideology continues to be.

 

This rather excited opinion piece by psychosocial enthusiasts is founded on getting the maths wrong.

Their great "insight" is that the association between MS and EBV is generally weak, and only strong for the 36 cases of MS who were EBV negative when they join the military and 35 subsequently became EBV positive prior to their MS. The authors conclude there is something about military service that dramatically increases the risk of MS.

According to these authors, the important factor is the odds ratio for those who were already EBV -positive when they joined the military. They calculated this as the 766 who were EBV+ at baseline/801 total MS cases, to give an odds ratio (relative to the control group) of only 1.6 (p <0.05).

But the point of the original study was to look at the risk of getting MS after EBV. So, for the MS cohort who were already EBV-positive at the start of the study, the relevant figure is 766/766, which leads to an odds ratio of about 25. There is no story here.

Of course, EBV is only causal in the sense that it appears to be a necessary step for getting MS. Almost the entire adult population has EBV, while the prevalence rate is only 0.13%. Other factors are clearly at play. Genetics is definitely one factor, others are up for grabs. But the authors of the opinion piece are getting carried away when they talk about "biosocial mechanisms: the next research frontier".

I think they might soon be suffering a hangover after the giddy euphoria of coming up with the idea and getting it published.

 

@Jacob Richter I'm part of World ME Alliance group WHO Group* I've been tasked with doing some research re ME/CFS like diseases**. I took the opportunity to flag up the potential to replicate the EBV/MS study i.e. ME/CFS - [EDIT - EBV] study. Funny enough one of the Solve reps is looking at the potential to link up with MS groups & they mentioned the EBV/MS study.
Not suggesting it will lead to anything though!
@ME/CFS Skeptic

*[Action for M.E. & Solve lead the group - I'm part of EMEC]

**https://www.s4me.info/threads/disea...ay-work-with-me-cfs-groups.30987/#post-453376

 

I agree it would be very interesting to further explore the potential links between EBV and ME/CFS, partly because my own ME onset was co-incidental with an active EBV infection, but also because active EBV infection is more likely to be associated with ME onset than many other viruses and EBV is so ubiquitous that many people have antibodies without ever being aware of an acute infection stage.