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

Main paper

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.

https://www.science.org/doi/10.1126/science.abj8222

Accompanying paper on the mechanisms

Infection with Epstein-Barr virus is the trigger for the development of multiple sclerosis

https://www.science.org/doi/10.1126/science.abm7930

 

New Scientist Strongest evidence yet that MS is caused by Epstein-Barr virus

quote:
It has long been suspected that the common Epstein-Barr virus can trigger multiple sclerosis (MS). Now, a study of 10 million military personnel in the US has shown that virtually every case of MS is preceded by infection with the virus. The finding suggests a vaccine against the Epstein-Barr virus could greatly reduce the incidence of MS.

 

If this hold up it will an important piece of information. It looks reasonably convincing to me.

I think it is a pity that anyone should cast EBV as a'leading cause' or 'trigger' for MS though. As I understand it is is an almost necessary permissive environmental factor. If I remember rightly certain histocompatibility genes are similarly almost necessary permissive genetic factors for MS.

There isn't really meaning to 'leading cause' in this context and we usually think of triggers as factors that trip the development of a disease at the time they are met. EBV infection is likely to have a permissive effect for ever after because of the way it persists in B cells.

It is perhaps surprising that EBV does not seem to confer this sort of major extra risk for all antibody-mediated autoimmune diseases (I take MS to be antibody mediated). Perhaps similar studies have not been done on large enough samples. But I seem to remember that a small proportion of people with diseases like lupus or RA were EBV negative at onset - and that the proportion was not very different from expected.

 

It might but there are some difficult unknowns. ebb infection in early adult life can produce complications that I think are much less common for infantile infection. If you vaccinate infants there may be an increase in cases in early adult life. There are similar issues around mumps and measles but different.

It might be more productive to develop a curative treatment for MS that can be given at the first episode. Curing disease like RA and MS should not be any more difficult than curing cancer, which is now routinely cured, but the motivation does not seem to be there. Chronic illness does not get the attention it deserves, as we all know.

 

Speaking of which, how are you doing with your Covid infection? I hope you're feeling better.

 

That sounds surprising! Why would it not be more difficult? Are the disease mechanisms understood and is it known what it would take to tackle them?

 

Talk about a needle in a haystack. This is why long-term research is critical, the hit-and-run model typical in chronic illness is simply useless for problems of this scale. Meeting large problems with small minds that easily get stuck in infinite loops and trip on their own ego is especially ineffective.

I don't want to predict too much here but it really looks like there's something to that old germ theory of disease. Damn, who could have known?!

 

I missed this. I also hope you are feeling better @Jonathan Edwards

 

A great many people that have been burried and ridiculed by the establishment.

 

I read that EBV infection early in life is less dangerous than in adolescence and later. The age at which EBV infection first occurs is also increasing. This could lead to an increasing incidence of EBV-related illness like multiple sclerosis or ME/CFS.

 

I don't think this has any implications for a 'germ theory of disease'.
Some germs cause some diseases - like TB and measles. Some don't. A role for EBV in MS would be an entirely unique mechanism almost certainly. It does not make any other germs any more likely to be causal for anything else.

 

I also believe that there is a cultural element for this very reason. I know that in Hungary most people never heard of EBV or mononucleosis unless they actually had it. I know I had no idea of their existence, had a hard time explaining even mono to quite a lot of people and also never met anyone else who had mono before I fell ill in my early 30s. (I think I heard about it in House MD but I only realized that in retrospect.)

My theory is that probably a higher percentage of kids catch it at a young age here, maybe due to sharing meals/drinks and other similar practices happening more often here and in turn, fewer adults catch it later since they had already had it as children.

Wikipedia actually confirms this idea: "Mononucleosis most commonly affects those between the ages of 15 to 24 years in the developed world.[8] In the developing world, people are more often infected in early childhood when there are fewer symptoms.[11]"

And I think this could maybe also partly explain why MS seems to be more common in certain geographical areas than in others.

 

https://www.nytimes.com/2022/01/13/...-barr-virus.html?referringSource=articleShare
Interesting similarities to ME in this quote from NYT article:

“People who develop multiple sclerosis have overactive immune systems that make them develop high levels of antibodies to viral infections. Multiple sclerosis might arise not because of the virus but because of the body’s response to it.

“Multiple sclerosis patients have fewer viral infections than normal,” he said, because their immune systems are so active that they effectively fight off viruses. “Multiple sclerosis patients often say, ‘I never get a cold.’ When I hear that, my ears perk up.”

 

Why would you want to open doors for biased researchers though!!
They are best kept out of research, as we have seen.

 

That doesn't really make any sense. If MS patients had less viral infections they would have less antibodies. Presumably they have the same number of infections and make more antibody. But it is the immune response that makes the antibody that producers the symptoms of viral infection so how come they have an overactive immune system but do not get symptoms?

And EBV is completely different from other viruses in this context because it alters the B cell population as a whole.

 

Both cancer and autoimmunity arise through cell mutations. The task is to get rid of the mutated cells. The mutations in cancer are outside any normal physiological mechanism and can lead to much moire severe problems with unregulated growth. But that in some ays makes it easier to pick them off selectively. In autoimmunity the mutations followed physiological rules and produce pathogenic clones that look fairly normal. They are less unregulated but they may be more difficult to target selectively for the same reason.

On balance the difficulty of the task is probably much the same. People like my brother, working on cancer, have worked out the mutations in detail for many types - breast, myeloma, leukaemia etc. The research is intelligent and well funded. In autoimmunity nobody much has taken seriously the biological detail. A few people have tried very aggressive treatment programmes - like Alan Tyndal's bone marrow ablation studies - but the research into the mutations is pretty much zero.

Interestingly, the cancer people were not that interested in the mutation details until about 2000 hen they suddenly realised that they could work out exactly what was going on using new techniques.

 

How would a virus like EBV cause the kind of metabolic alterations seen in ME/CFS? My understanding is that only a small proportion of cells in the body are infected. The metabolic alterations in the infected cells would not be noticable with metabolomics analysis. Instead what metabolomics shows is mainly the consequences in the rest of the body.

 

Re the symptoms: perhaps like ME patients they don’t have the usual response to a virus (sniffles etc) but do have an ongoing fatigue / PEM bc of going immune dysregulation. I remember Ron Davis tried to talk with a lot of MS doctors and realized many of their symptoms had overlap with ME. His point to them was that ME could be a part of MS or a pathological state separate to MS that happens concurrently with it..? (I’m not sure how to describe this properly)

 

I am not sure we know of any metabolic alterations in ME. There are some papers on metabolic changes in peripheral blood cells that are part of the immune system but I am not sure that they tell us much.

If EBV as relevant to ME it would probably be through allowing an immune response to occur that generated signals like those in infections that alter our metabolism through making us feel ill.

 

Personally I don't think any overlap of symptoms tells us anything. Both Diabetes and methanol poisoning can make you blind but that does not mean they have anything in common. We know exactly why people with MS have the specific symptoms they do (demyelination) and there is no demyelination in ME.

I am pretty unconvinced by the stories about having more or fewer infections in illnesses like ME. It is a bit like saying that 50% of people are below average and 50% are above average on something - they always are.