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Multiple Sclerosis Causality

606 points1 dayscience.org
dm31923 hours ago

Here's a link to the article [0].

Just a bit of background - 95% of humans will experience infection with EBV at some point in their lives. Once you're infected, it remains latent, only flaring up in particular circumstances. MS is an autoimmune disease, like many others, and this paper does not imply that EBV directly causes MS. Obviously, as so many more people have EBV than have MS, EBV infection does not completely explain why people get MS.

Just to put a small caveat to the paper. The comparison is to EBV 'seronegative' population - this is a minority of people (i.e. people who do not have evidence of being infected with EBV). You could argue this is an 'unusual' population in the first place and there's something about them that provides protection from MS.

Another point is that EBV is a risk factor, there are other risk factors known too. I think the key to understanding a lot of autoimmune diseases is to understand how our adaptive immune system works. Our immune response is a very complex cell-to-cell interaction between millions of cells all with different roles, and how the immune system decides whether something is a threat or not is not, and how to respond to it, is not yet clear.

[0] https://www.science.org/doi/10.1126/science.abj8222

dekhn23 hours ago

At least part of the adaptive immune system is implemented in the thymus. As an infant, the thymus makes examples of nearly every type of cell in the body and uses it as negative labelled examples to tune the false positive detector so it doesn't identify self as threat. From an information theory perspective, that's pretty extraordinary (you don't normally expect differentiated cells in an organ to act like cells from another organ).

Another part of the adaptive immune system randomly shuffles different regions of genes together to produce enormous diversity (searching for a rare example of something that "works"), then picks the proteins from those genes that work best and distributes them throughout the body.

Pretty amazing stuff.

dm31923 hours ago

Yes, it's really fascinating stuff. Just to add to that, cells must present a continuous sample of their proteasome on the cell surface in the form of a short peptide 9-12 amino acids long. T cells will recognise when the cell is producing protein it shouldn't be (i.e. because it became cancerous or infected with a virus), even if only one amino acid is incorrect.

It learns this in the thymus, which has a bizarre gene called AIRE which switches on genes from all over the body, essentially creating a representation of the entire body in the thymus gland as a sort of sandbox before they are let out.

However, we don't have enough T cells to recognise every possible sequence of 11 amino acids (which would weigh around 1.5 tons), so T cells must be so-called 'cross-reactive'[1]. And therefore other factors must go into how T cells respond to abnormalities.

[1] https://www.nature.com/articles/nri3279

dekhn21 hours ago

yep, i was referring to AIRE without naming it. I saw a talk about it years ago and it blew my mind. In retrospect, it seems to just sort of fall out from the way you'd expect adaptive immunity to evolve, though.

hallway_monitor20 hours ago

I don't see many YouTube links posted here, but this Kurzgeasgt video blew my mind on this topic. Our immune system really is amazing.

https://www.youtube.com/watch?v=LmpuerlbJu0

+2
whatshisface19 hours ago
mdswanson20 hours ago

Can't help but to highly recommend the recent book by Philipp Dettmer, Immune: A Journey Into The Mysterious System That Keeps You Alive. It's fantastic and very readable: https://www.amazon.com/dp/B08XTNHRR5/ref=cm_sw_em_r_mt_dp_FX...

rubicon3352 minutes ago

Where can I read more about this? Can you recommend a book or something?

whatshisface23 hours ago

What's the connection to information theory?

d0mine12 hours ago

On information theory [unrelated to the discussion]: both digital information (stored in DNA --4-letters) and analog information (epigenome) can be manipulated for various effects e.g., "Lifespan: Why We Age—and Why We Don't Have To" by Sinclair https://www.amazon.com/dp/B07N4C6LGR/

dekhn23 hours ago

sorry, I shouldn't have thrown that in there.

jonnycomputer23 hours ago

I think this is may be one reason they used CMV infection as a control. Unless you think that the people who don't get CMV are not special, but the ones who don't get EBV are...

dm31922 hours ago

Yes that's a good point.

moneywoes23 hours ago

As someone with an autoimmune disease, is there anything I can do to prevent getting more? Iirc having one is a risk factor for others

kortex1 hour ago

Helminth therapy is supposed to help moderate it. I did it to get a handle on my asthma and allergies and it worked quite well. There's various websites and support groups which detail the process and why it works etc.

There's a bit of squick factor to get over but it is worth it for the relief.

https://helminthictherapywiki.org/wiki/index.php/Helminthic_...

kennethh10 hours ago

I had Ulcerative colitis for 20 years and managed to get rid of it by changing the diet. I used the carnivore diet, ie eat mostly meat, egg, fish (animal products). Cutting out processed foods, sugar (only 70% dark chocolate) and seed oils. I would recommend trying it for a couple of months and see if it helps, and if you do not notice any difference you have not lost anything. I lost 10% of my body weight without ever being hungry so that might be a nice side effect also.

mb_729 hours ago

Crohn's sufferer here. I have lost track of the times people have said "I tried this diet, and then my Crohns / UC went away".. and then some time later their symptoms reappeared. My understanding (via own reading and discussion with my doctor) is that there is just as much evidence against as for a meat-based diet .... or any kind of diet.

As my specialist put it "if there was a common diet that cured people, we would know about it already". Anecdotally one never knows if their UC/Crohn's improves because of their diet or it's just part of the ups and downs of those diseases.

That said, I'm happy in general if I hear a fellow UC / Crohn's sufferer seems to have found something that works for them, especially something that is better for you than steroids and other treatments with severe side-effects.

jopsen6 hours ago

Yeah, it's also my take that one should be careful correlating ups and downs to things eaten -- it might as well be stress or just bad luck.

That said, if I can get some placebo effect benefits from believing that reducing processed food helps, it might be worth doing -- if nothing else it reduces cancer risks :)

Broken_Hippo9 hours ago

To be absolutely fair to readers: Please speak to your doctor before deciding on a diet to "cure" an illness, especially since fatty foods can trigger attacks for some folks. Ulcerative colitis has no actual cure, and this is one way one person has managed it a bit better. It might not be recommended for you.

(Sorry, i'm in this thread because I have MS, and there are lots of scam diets claiming to cure it. They don't - at all. They mostly just make folks feel like they have control).

dncornholio6 hours ago

Carnivore diet seems like a perfect excuse for people who don't want to eat their veggies. If you could provide any proven benefits of this diet that other diets don't provide, I'll change my mind.

dm31922 hours ago

I'm afraid this is out of my scope of understanding. Once the immune system determines something is non-self, the immune system can often self-propagate the response. It eventually enters a tolerance phase where it aims to just 'control' the threat.

There are some known modulators of the immune system, but the medical forms can be especially blunt tools (i.e. steroids). Locally directed treatment is better, and maybe in the future we'll have specially crafted cells that can inhibit a specific response for particular antigens.

There is a long and slightly-controversial link between stress (and lots of other environmental factors) affecting the immune system. I'm not familiar with the literature.

manwe15013 hours ago

I recently learned (also from HN) that wild-type measles can often destroy your bodies pre-existing immunities to most past threats. I wonder if we will someday be able to trigger a similar effect with a synthetic virus, wiping the immune memory, then re-vaccinate to get back immunity afterwards. But it is practically just science fiction stuff now, as far as I know.

Broken_Hippo9 hours ago

Nope. Since we aren't certain what causes most things, we can't really prevent them. (This research isn't saying they know what causes MS, to be clear).

Realistically, the best thing you can do is basic health stuff. Get activity, eat a variety of healthy foods, and so on. As you can, anyway. Mostly because this stuff improves your outcome if you happen to get another (and probably helps with the one you have - I have MS, and this basic stuff tends to help outcomes)

mpreda21 hours ago

[this is not medical advice] Some things that may modulate the immune system are: vitamin D3, intestinal worms, exercise, diet / fasting, and gradual stimulation of the immune response ("desensitisation").

trulyme11 hours ago

Off-topic: interesting that we often see IANAL, but very rarely IANAD (I am not a doctor) around here. Either there's a lot of doctors here, or people are more comfortable giving medical than legal advice, which is weird, as medical advice can have very serious consequences.

pbhjpbhj9 hours ago

I think it's just default recognised that you're not getting a doctor's medical advice, particularly not for you, through an internet forum. So, someone would have to tell you they are a doctor, and you'd still not get their medical advice unless you had a consultation with them. That last bit being similar to lawyers reminding people "IAAL but I'm not your lawyer".

johnisgood13 hours ago

Propolis and Cinnamomum verum are great immunomodulators for autoimmune diseases. Echinacea is sold as an immune system booster, and it is a firm nope.

hda1119 hours ago

Had a similar thought when reading the headline. It’s like saying drinking water causes MS.

philshem7 hours ago

100.0% of people consume H2O. There is no control group.

birdyrooster17 hours ago

I guess titling the article "Multiple Sclerosis Causality" and then immediately going into EBV correlation seems like implication to me.

user9034908318 hours ago

For anyone dealing with an acute bout of Epstein-Barr Virus, I used 3 teaspoons a day of monolaurin for three weeks to kick it. Research monolaurin, it's fascinating stuff as an antiviral and I can personally attest to its effectiveness.

csdvrx18 hours ago

Or get actual antivirals. IIRC the same thing that's prescribed for HSV works on EBV

user9034908316 hours ago

Some people prefer God's medicine to man's medicine. To each his own

dtech6 hours ago

I never understood this argument. If God was against these medicines, why would He allow them to exist?...

+1
taneq16 hours ago
Mezzie23 hours ago

I have MS and my first relapse was a pretty textbook case of transverse myelitis of the sort that the EBV can cause.

I know some people have been asking about why that might be the case when a ton of people have EBV, and I think the causality may go the other way: Those of us with something wrong are more likely to both have EBV complications and MS.

There are other viruses like this as well (ones that most people get/have but aren't dangerous). I was on one medication where I needed to be tested monthly because if I got one particular (normally harmless) virus, the suppression caused by the medication meant I would probably die.

There's pretty clearly some sort of relation between the state of one's immune system + how it deals with 'benign' viruses + auto-immunity, and I'm excited to see what the future holds, but for now it's a cool confirmation of something a lot of MSers have talked about amongst ourselves for a while.

jessriedel21 hours ago

> I think the causality may go the other way: Those of us with something wrong are more likely to both have EBV complications and MS.

I'm unsure, but it sounds like you're hypothesizing that EBV infections does not cause MS symptoms, and that instead some some third factor causes both, so that preventing EBV infection would not prevent MS. The paper being discussed specifically considers and rejects this possibility with pretty strong evidence. Indeed, that is the main contribution of the paper. (The fact that 99% of MS sufferers have EBV, way higher than the 90% baseline in the general population, has been known for a while.)

Mezzie19 hours ago

That's why I shouldn't read articles instead of taking a nap. Thanks!

loudtieblahblah6 hours ago

There's other factors too.

All MS suffer-ers have low VitD.(as does just about everyone with an autoimmune issue).

They all have low uric acid too.

Almost all MS sufferers (same more most autoimmune) can also trace their disorder back to an extreme stress event too - divorce, loss of a loved one, falling into health anxiety, etc..

Are these causes or effects?

I'm guessing there's compounding factors.

csdvrx18 hours ago

Or that people who can't clear EBV may be unable to due to some deficiency that also cause them to get MS

Still a super interesting paper

roganartu21 hours ago

> There are other viruses like this as well (ones that most people get/have but aren't dangerous). I was on one medication where I needed to be tested monthly because if I got one particular (normally harmless) virus, the suppression caused by the medication meant I would probably die.

For those curious, I’m going to guess and say this might’ve been Tysabri (natalizumab) and that the virus in question is JCV (John Cunningham virus). After approximately two years on Tysabri, people who test positive for JCV antibodies (approx half the population of the US) have an extremely high chance of developing an often-fatal brain infection called PML (Progressive Multifocal Leukoencephalopathy).

Tysabri was originally pulled by the FDA due to PML deaths back in the early 2000s, but later got reapproved after the link to JCV was discovered. Nowadays patients get tested for JCV antibodies every 6 months. The treatment is considered quite safe now, with the caveat that if you test positive you cannot get Tysabri anymore. Most people don’t switch from negative to positive, but it happens occasionally.

Source: my wife has a rare form of MS and has been on Tysabri for about 5 years now, relapse free. Modern MS drugs are a scientific marvel.

2dvisio17 hours ago

Confirm. My brother is was on Tysabri for more than 5 and recently got confirmation of JCV. The checkup is however more regular. Blood test + MRI + symptoms check every three months, as if done less regularly would increase massively the risk. If JCV flare up is detected they’ll need to flush/wash the Tysabri away from his bloodstream.

He also got a severe mononucleosis infection before being diagnosed, and at that time we all thought that could have been the cause.

loudtieblahblah5 hours ago

Monthly 3-4 day fasts - combined with a healthy diet in between (Mediterranean for ex) do wonders for autoimmune issues as well.

It was found fasting kills off old immune cells and activates stem cells to make new ones.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474734/

https://pubmed.ncbi.nlm.nih.gov/31442401/

https://www.nejm.org/doi/10.1056/NEJMra1905136

http://www.cell.com/cell-stem-cell/abstract/S1934-5909(14)00...

In plain English

https://www.forbes.com/sites/stevensalzberg/2014/12/30/can-a...

https://www.medicalnewstoday.com/articles/277860#In-mice,-pr...

Mezzie19 hours ago

Bingo!

Broken_Hippo9 hours ago

To be fair: I have MS. I've never had EBV with symptoms that I know of - which is absolutely normal. When folks catch it as children, there are generally zero to no symptoms. And I'm not alone, judging by activity on MS related sites.

I wouldn't take the word of "a lot of MSers" - I mean, there are folks that push the scam WAHLS protocol (diet) as a cure, too. Unless the folks are researchers, an MSer's thoughts about what causes the disease are often just as baseless as a non-MSer.

dtech5 hours ago

> I think the causality may go the other way

The whole point of the article is that this isn't the case.

supperburg17 hours ago

Well said. I said the immune system should be to blame in the previous thread and was downvoted to hell. But it’s true. What’s more, it’s highly under appreciated that the immune system is extremely ancient and it does a lot more than the typical things associated with it like destroying tissue. It pulls deep metabolic levers that can make critical cells, including brain cells, latent. It can do many amazing things. In the future, the immune system won’t be known for immunity — it will be known as something like the second nervous system and will be associated with the nth great wave of medical progress when we finally conquer it and all the hundreds of diseases it causes. Diseases we don’t even have a name for now, I know for a fact.

the_decider12 hours ago

An immunological biomarker aasociated with MS had been discovered a few years back, but sadly nothing came of that research. https://www.nature.com/articles/s41598-017-04439-5

supperburg4 hours ago

I think even if we find some markers it won’t be enough. It will take a full blown revolution in how we measure human anatomy in a clinical setting. That’s why it’s taken so long.

brechmos22 hours ago

What is interesting is that Epstein-Barr has been reported to be related to Multiple Sclerosis since the early 1980s.

https://pubmed.ncbi.nlm.nih.gov/?term=epstein+barr+multiple+...

It is great if there is new information and if this leads to knowledge on how to reduce the chance of getting MS.

sonicggg23 hours ago

Cause is still not well explained. EBV is such an ubiquitous virus, more than 90% of all adults worldwide have been infected with it. Most will never know. Why is that just a tiny percentage develop MS?

malloc204817 hours ago

Good question, if I am correct there is also a higher chance to develop MS if you are a woman and if you live in the northern hemisphere and some parts of Australia and New Zealand.

Also if you are of Northern European descent the risk is higher if I remember correctly.

Possibly it's a mix of many things and you have to be one of the unlucky people where that mix triggers something in the immune system and the disease develops.

I am very unlucky in that regard.

According to my doctors the number of autoimmune diseases I have is rare in a single person.

I have a sysmetic autoimmune disease (Rheumatoid Artritis) and autoimmune diseases in my kidneys, liver,thyroid, skin and mouth.

So somehow multipe times there were events in my life where a mix of things caused my immune system to turn against me.

A little off-topic, but to give an impression of how that works out in daily life, in case you are also diagnosed with an autoimmune disease.

If you are lucky, there is good medication and you will hardly notice you're ill, except for the checkups with your doctor

I also know some autoimmune diseases can (become) pretty aggressive, but n=1, most people I know with autoimmune diseases have a decent quality of life.

Fortunately, in my case also for each disease there is medication that either supresses the inflammation or the protects my body against the effects of the auto-immune response.

So I take my pills and a bi-weekly injection with a biological and I can continue to live with a decent quality of life.

Except for one important thing, my main remaining symptom is that I have a lot less energy than most people and need much more sleep.

Despite that all inflammation parameters in my blood show no signs of inflammation or activity of the disease, my body somehow loses energy to something.

This seems to be a complaint of many autoimmune illness sufferers, no signs of activity of the ilness, but more tired than before the disease came into their life.

Hopefully there will soon be more developments in this area of medicine.

someotherperson7 hours ago

> if I am correct there is also a higher chance to develop MS if you are a woman and if you live in the northern hemisphere and some parts of Australia and New Zealand. Also if you are of Northern European descent the risk is higher if I remember correctly.

I believe this has been largely disregarded. The higher incidence rate in Europe/Anglosphere was a consequence of higher testing and accurate diagnoses, coupled with the ability to provide treatment.

supperburg17 hours ago

Yes, inflammatory signals can and do pull metabolic levers, something that is criminally under appreciated, and this can manifest as feeling tired somehow. There is absolutely a connection.

killjoywashere23 hours ago

EBV is associated with a lot of things that involve a tiny percentage of the population. Nasopharyngeal carcinoma, Hodgkin's lymphoma. Non-Hodgkin's lymphomas. Post-transplant lymphoproliferative disease. Burkitt's lymphoma. Oral hairy leukoplakia. Related viruses are associated with other diseases, e.g. HHV-8 and Kaposi's Sarcoma, primary effusion lymphoma, and Castleman's disease.

jessriedel22 hours ago

Is there an estimate anywhere of the total health burden of EBV, making reasonable assumptions about causality for the diseases you describe? Would be very interesting to know so you could compare it to the risk of a future EBV vaccine.

Metacelsus21 hours ago

I calculated it on my blog a few months ago: Every year, it causes the loss of 4.6 million disability-adjusted life years due to cancers alone, and another ~2 million to autoimmune diseases like multiple sclerosis.

https://denovo.substack.com/p/epstein-barr-virus-more-maladi...

throwawaylinux17 hours ago

What are the reasonable assumptions about causality?

rewgs14 hours ago

Welcome to the immune system :p

Most people don't develop food allergies. Especially most adults if they don't have a family history of it/didn't have any food allergies as children. Those that do typically only develop 1 or 2.

I can't imagine how infinitesimally small the odds of this happening to me are, and yet here I am, at age 31, with nearly 30 food allergies that all activated about a year ago, seemingly overnight. No known cause, and after a year of researching the immune system and just how depressingly little medical science knows about it, I doubt I'll ever know, let alone receive a treatment that will allow me to eat like a normal person again.

And that's just one way in which the immune system can go haywire. There's MS and all the dozens of other (auto)immune issues -- so many that some don't even have a name. It is truly baffling, but the immune system has gotta be one of the single most complex systems known to man. There's a whole lot of ways something like that can break.

dd366 hours ago

Pardon my ignorance, does this mean you won’t have allergies if you take an immunosuppressive drug?

scotty7912 hours ago

Why only a small percentage of those who contracted polio got paralysis? Interesting, but for now let's settle on eradicating ebv to hell

jessriedel22 hours ago

This question, though very worthwhile, doesn't necessarily need to be answered. Vaccines for EBV are under development. If we stop most EBV infections, we can stop most MS.

lamontcg18 hours ago

Doesn't help you if you've already got a persistent EBV infection though, and the host immune response to EBV may be something that you want to avoid stimulating if you've already got it in you and can't get it out.

Something like CRISPR/Cas9 editing may be the way to treat persistent EBV and other herpesvirus infections.

bluGill16 hours ago

Maybe, though it appears that covid vaccines help clear long covid, so maybe not. Until we have a vaccine we cannot study this to see how or if it works.

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lamontcg16 hours ago
Metacelsus21 hours ago

Yeah, but will the vaccines be effective? EBV is amazingly good at immune evasion. Prior antibodies don't protect against re-infection.

sonicggg21 hours ago

Vaccine is no guarantee though, just look at Covid. DW was recently covering breakthrough cases that led to Long Covid. You're speculating now.

boondaburrah20 hours ago

Right but when was the last time anyone you know got polio? Vaccines aren't 100% effective but if we can get the average susceptibility to the virus in the population down far enough (even though it'll never be complete) there's a threshold where the virus can have a hard enough time hopping that it really makes a difference.

bagacrap15 hours ago

I don't see where gp assumed a vaccine will be effective. Note "if".

reedf11 day ago

Terrifying - I was EBV positive 4 years ago. It does not mention an association between EBV severity and MS, but I was very symptomatic and had post viral fatigue for around a year. I had no idea about the MS association!

danuker24 hours ago

> According to epidemiological studies, the EBV is estimated to be positive in more than 90% of the world's populations

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008310/

> A total of 2.8 million people are estimated to live with MS worldwide (35.9 per 100,000 population)

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720355/

Given that you have EBV, I guess you're in the unlucky 90%, increasing your odds from 359 in a million to a ...whopping... 399 in a million.

BobbyJo23 hours ago

Since the risk for the non-EBV group is 32x less, you'd be increasing your odds from like 11 in a million to 399 in a million no?

andi99923 hours ago

If you knew you were negative yes, if the status was unknown then not.

arbuge24 hours ago

Calm down... from the article:

"Note, though, that EBV would then be in the "necessary but not sufficient" category. There's something about the interaction of particular human immune systems with EBV infection that pushes things over into the pathological state of multiple sclerosis, and we don't really know how to identify these people. But that fits with what we know about infectious disease in general - everyone's different. The situation with Guillian-Barré is similar - a small number of people tip over into neurological pathology, for reasons unknown, and that one also often seems to follow some sort of viral infection."

jka24 hours ago

That's a good quote, thank you.

About the use of "calm down" as an instruction: while your sentiment is good (to reduce another person's anxiety), it's not always possible for someone to follow that when it is received as an instruction. It's tricky to estimate other people's emotional state based on text, and for them to infer your tone. I'm overexplaining and sure that you probably understand all that; but it feels worth mentioning.

dwmbt23 hours ago

> About the use of "calm down" as an instruction: while your sentiment is good (to reduce another person's anxiety), it's not always possible for someone to follow that when it is received as an instruction.

this is a pet peeve of mine. something i picked up when i was a counselor at a special needs camp was the idea that everyone (regardless of where you lie on any spectrum) has a unique sensitivity to criticism. it's important to NOT treat people how you would like to receive criticism, but to assess how you think they would best consume and digest it. obviously, this is extremely difficult on the internet and i'm just nitpicking but i had an altercation with my sibling earlier when they told me to 'calm down' so i'm still on edge about it.

i'm sure OP doesn't need to hear this but typically i find that a good alternative is to nudge someone into rationality. not to say that the parent comment is irrational, but when you simply show someone why they may be overreacting, they may very well 'calm down' all by themselves. if said person refuses to acknowledge your rationale, it's likely they aren't welcome to any criticism at all and won't be 'calming down' in any capacity.

jonnycomputer23 hours ago

True. My first reaction to the directive, was that it was rude. Reading more of the context attenuated that impression, but I still think it could have been phrased less ... paternalistically?

+1
jka23 hours ago
garganzol24 hours ago

There is one more condition you may be interested in: CFS/ME. It manifests itself primarily as a chronic fatigue and is believed to onset after a trigger event: virus, intoxication, hypoxia, stress, and the like.

I talked to some people with MS and most of them told me the same story: the trigger event, followed by some time, then onset of a full-blown MS.

I wonder: are those diseases really different? Or maybe this is the very same disease but with a bit different outcomes: myalgic encephalopathy vs sclerous plaques. Both are driven by the inflammation, both have the same initiating sequence.

What leads me to strongly suspect that it may be just different manifestations of the same disease is the involvement of mitochondria in both MS and CFS/ME.

kennethh9 hours ago

In Bergen in Norway we had a big outbreak of Giardia parasite and a lot of people got CFS/ME after that. The Giardia was big because the parasites came into the drinking water from one of the water sources. I myself had this for of this for many years afterwards but one do not notice it since before you get rid of it. I was able to function normally but totally lacked energy, and everything was a chore. It was like the feeling the first time one drinks coffee and experience the way the fog clears up.

Conclusion. The study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection. Obstructive sleep apnoea/hypopnoea syndrome, depression and anxiety were important differential diagnoses, or possibly comorbidities, to post-infectious fatigue in this study.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598369/#:~:tex....

Also very impressed with google when searching for: giardia leads to CFS

thewebcount20 hours ago

And along with CFS/ME, also look up POTS, MCAS/MCAD, and EDS. My wife had a very bad bout of mono in late high school and 15 years later developed POTS, MCAS, and what the rheumatologist called "unspecified connective tissue disorder," which seems like a mild case of EDS. After 10-15 years of trying treatments, she's significantly worse off. :-/

There are tons of people (mostly women) out there with this set of conditions, and they're only starting to be taken seriously. It's a set of life-altering conditions and dealing with the medical system when you have it can be infuriating and exhausting. I hope you don't have any of these things.

garganzol7 hours ago

POTS, MCAD-like (hyperlipidemia) and inflammatory conditions are triggered by CFS/ME as well.

I am really puzzled: are we dealing with the same thing but under different names?

For reference, NSAIDs combined with high-dose vitamin therapy help to resolve those conditions in people with CFS/ME.

mturmon15 hours ago

My wife also has MCAS, POTS, and a connective tissue disorder that is not at the level of EDS. Was diagnosed about 4 years ago and is on treatments to suppress some immune responses, that has been helpful at taking the edge off some symptoms. It was like tumblers clicking into place when she saw a specialist and got the diagnosis, so many rather disparate, long-term symptoms all from the same cause.

radicalbyte22 hours ago

I have this pet theory that CFS/ME is what a lot of long-covid patients are suffering. I knew a few people who have been affected by it, and it really limits them. Just as long-covid seems to.

garganzol21 hours ago

I came to the same conclusion as well. Moreover, I was somewhat successful in healing post-viral CFS/ME using the therapy targeted at mitochondria with large doses of B1 and B3 vitamins [1].

[1] https://news.ycombinator.com/item?id=29138006

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PaulKeeble19 hours ago
+1
csdvrx17 hours ago
rmind21 hours ago

Back in 1980s, there were proposals for a "chronic mononucleosis" or "chronic mononucleosis syndrome" as a diagnosis / standard disease. There were very comprehensive studies trying to investigate the patients who had chronic fatigue and other long lasting debilitating symptoms. After a good decade of studies, the research community found that this group of patients is very consistent (their complaints, symptoms, etiology), but failed to prove EBV as a cause (although the studies did not disprove it either) or at least come up with a clear serological diagnostic criteria. So, in 1990s they decided to define a generic Chronic Fatigue Syndrome (CFS) as a standardized disease. Other viruses and pathogens can cause CFS/ME and a broader definition would sometimes include even psychosomatic patients, so as a result CFS/ME has been quite discredited.

Diagnostic techniques evolved and research progressed. In the recent decade, new studies are very close to proving that EBV is indeed a likely cause of CFS/ME (well, one segment, as there are other causes too). Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912523/

lalaland112524 hours ago

One important thing to note is that EBV is extremely prevalent. Almost everyone gets it eventually and very few of those people develop MS.

jonnycomputer23 hours ago

But a lot of people don't really develop severe symptoms either, right?

marvin22 hours ago

When I had it, my doctor said that if I was a professional athlete, the standard outcome would be to just consider the current season lost and switch focus to getting well again in time for the next.

I was relatively useless for two weeks and then spent the next four months getting back to my normal energy levels. "Severe" is a question of definitions, I think. I wouldn't consider that kind of illness severe, but it certainly put a dent in things for a while. Properly inconvenient, I'd say. I think this degree is pretty common.

cestith21 hours ago

Some develop no noticeable symptoms and many develop mainly annoying ones for a few weeks to a few months. I had the misfortune to develop symptoms from infectious mononucleosis shortly after minor surgery. My GP and surgeon kept giving me antibiotics and sending me back to uni. Finally after several months of fatigue, nausea, and depressed appetite I wandered into campus health jaundiced with a 104º F fever and a temporarily enlarged liver. I ended up withdrawing from that semester and retroactively from the previous one. I was ordered into a month of bedrest and half a year of decreased physical activity while recovering. So I guess we could say there's a wide range of severity, partly depending on how soon it's addressed.

Broken_Hippo8 hours ago

Many if not most folks dont' even realize they get it because they catch EBV as a child. In children, it generally causes no symptoms or symptoms so mild that they are dismissed as a normal childhood virus. You know, the sort you miss 2 days of school for and then go on. This is the reason most folks don't know they've had it.

When we get older - teens and adults -, we are more likely to have it develop into mono or other things that realistically make your life difficult for a while.

cjensen20 hours ago

EBV causes more severe symptoms the older you are. So everyone here who remembers getting it and it being terrible? That's because you got it as an adult. If you get it as a kid, it can be asymptomatic.

I got it at 36 and had a fever that leveled me for 3 weeks. Between "wait 1 week before bothering your doctor" and multiple rounds of tests, they didn't even diagnose it as EBV until the 3rd week.

csdvrx17 hours ago

I got at 21 IIRC and I was in bed for a few weeks and the doctor started fearing I had a blood cancer or something given how abnormal the tests were until he finally got the idea to test for EBV and it came back super positive.

Never before was I so happy to get tested positive for something lol

It's been a few years and I think I'm fine but due to hedonic adaptation etc maybe for all I know I operate at like 70% of my previous capacity and don't even realize it

So I'm super interested in all that new research and I can't wait until we get mRNA vaccines against EBV!!

RspecMAuthortah23 hours ago

How do you even test for EBV? The GP I asked laughed it off when I was living in Canada basically saying I am already positive and no need to test.

rmind21 hours ago

If you want to test whether you already had EBV, then it would be a test for Immunoglobulin G (IgG) antibodies to the EBV viral capsid antigen (VCA). It shows whether the virus has established the latency in your body. Most laboratories would just label it as "EBV IgG", so just ask for that.

If you are in your 30 or older, then you most likely have had it already.

panabee19 hours ago

thanks for sharing.

does this test for EBV in both latent and lytic phases?

EBV seems very adept at evading the immune system. does this also impact our ability to perform accurate detection (i.e., could current methods yield false negatives)?

csdvrx17 hours ago

They have like 2 separate tests: one for old EBV (IGG) and one for new EBV (IGM or maybe it's the other way around?)

IDK about false positive though

cestith21 hours ago

There are at least two tests for it, or at least there were in the mid 1990s. One's a quick clinical test with lots of false negatives than can be done in-office but unless it's a campus healthcare clinic at a university they probably don't bother. The other is a more sensitive lab test that takes a few days. If you're having a really serious set of symptoms they may test to confirm it's not something else. If it's a minor case, two weeks of bedrest fix a lot of issues in a young adult and you do probably already have it anyway.

currency22 hours ago

This was a study conducted by the military on soldiers. They all contributed three blood samples over a period of time that were tested for a large number of conditions. EBV was the only one that contributed to MS.

epgui22 hours ago

You can test for pretty much anything in a research setting.

In a clinical setting, doctors will rely a lot on heuristics and practical considerations, and there may not be any clinical testing available.

bluGill16 hours ago

Even if there is a test, sometimes it is insanely expensive and so they won't give it if they can find any other way to decide.

MaximumYComb22 hours ago

Wow, I was also EBV positive ~4 years ago (45 months), was symptomatic and I had post viral fatigue for around a year. It was 12 months before I could do light physical training and it was around 2.5 years before I could train physically at high intensity.

csdvrx17 hours ago

Do you have a baseline to compare or are you only relying on your memory?

I got it at 21 and now I fear I may operate at a lower overall potential since I don't have a baseline to compare to

shadowgovt23 hours ago

If you're EBV-positive, you're in good company... It infects something like 90% of the human population.

Makes me wonder how many virii are out there that haven't been identified by modern medicine because their spread vector is so low-impact that they never even trigger symptoms. A virus like that would become real indistinguishable from "behavior of the human body" in not very much time if its infectivity was high.

csdvrx17 hours ago

> A virus like that would become real indistinguishable from "behavior of the human body" in not very much time if its infectivity was high.

My weird theory: how can we know then if aging (or its acceleration or the diseases usually linked to it) isn't the result of some infection that's super contagious and infects 100% of the people,

raylad15 hours ago

It's not weird, it's the same idea I had back in the 1970s, but at that time things like retroviruses weren't known or understood.

Now we know about endogenous retroviruses, and yes, they have infected everyone (going back millions of years) and yes, they do become more active in aging and are responsible for cancers and causing cellular senescence via DNA damage through retrotransposon activity.

You can inhibit them with some of the same anti-retrovirals that work on HIV. Or nutritionally what may work is: high doses of cyanidin plus NAD precursors to stimulate SIRT6, which normally prevents at least one of these endogenous retroviruses, LINE1, from being expressed.

csdvrx10 hours ago

Super interesting. Please tell me more, like what you are taking besides that.

I find it especially interesting how some multicellular macro organisms like jellyfish (one of the oldest ancestor of all non insect animals) have no aging, while humans and most other animals do.

Could it be that their immune system or simply their evolutionary path prevented them from being exposed to such endoviruses, that may simply be too omnipresent (or long integrated) in about every other species to be selected out? (They could also present an advantage at the population scale, by ensuring a quick turnover and therefore more genetic evolution simply by filtering out not just the unadvantageous gene but the older adults, thus offering more opportunities for the new generation to replace them faster)

This could be supported if jellyfish had less requirements for evolution, like a stable ecological niche - something I have no idea about!

inter_netuser10 hours ago

Because it's very unlikely the same pathogen or disease would affect shrimp and humans in the exact same way.

axg1123 hours ago

Great question. A related question: how many undiscovered viruses exist that are beneficial to the host?

bigbillheck20 hours ago

There's the anelloviruses which are at least as prevalent and nobody really knows what they do.

nefitty24 hours ago

The article says EBV is prevalent and is probably necessary but not sufficient for MS. If I was in that position I would look at my gene test results for any markers that correlate with MS. The more of those markers, the more intensely I would prioritize following relevant interventions.

nradov24 hours ago

What are the relevant interventions? Which genes correlate with MS?

nefitty23 hours ago

That's the independent study part. I wish I could be more help but that research is time and money intensive, and not guaranteed to be fruitful. It also involves review of multiple studies, sometimes several dozen. Then it's about seeing which ones are relevant to an individual's specific genetic mutations.

I'm currently going through dozens of reports from SelfDecode, and that's after massive amounts of work on their end. I think I'm out a few hundred bucks so far, but it is an amazing service. I will soon seek their genetic consultation service, which is about $1k, and their lab testing service.

mwint18 hours ago

Genuinely curious, what's your ultimate goal here? What do you optimize for? Total life-years, sum quality-of-life, etc.?

Seems like picking out the diseases you don't want to get/die from is a way to go nuts; curious how you're thinking about this.

f38zf5vdt24 hours ago

If you're going to develop MS as an adult after getting EBV mononucleosis, it's likely that it will be soon (5-10 years) after you have the initial infection as an adult. There's only a long delay in children according to one study. [1] Every passing year the probability of getting MS should decay after that.

Female sex and EBV mononucleosis during adolescence are the biggest risk factors.

[1] https://nn.neurology.org/content/4/3/e308

Broken_Hippo8 hours ago

Scores of folks with MS never had mono. I'm one of those. It isn't mono that is the risk factor, but EBV itself.

config_yml20 hours ago

Interesting. My sister and I both had mononucleosis before puberty, and she was diagnosed with MS in her late twenties.

peter30322 hours ago

Possibly a co-factor, since many get EBV and few MS.

Severian23 hours ago

Found this in my news feed, so this timely. Good news I guess!

https://www.forbes.com/sites/roberthart/2022/01/14/moderna-s...

Miner49er22 hours ago

Is there any evidence that the vaccine wouldn't also cause MS? From my understanding, MS is caused by the immune response, and the vaccine would trigger a similar (or same?) immune response.

Miner49er23 hours ago

From my understanding, the leading theory of what causes autoimmune diseases is viruses. The immune system responds to the virus and ends up mistakenly attacking the body as well. This seems to support that, and shows that different viruses cause different autoimmune diseases.

More info: https://www.nature.com/articles/d41586-021-01835-w

f6v22 hours ago

I’ve been reading recent research on MS and other autoimmune conditions. I also study APS1 in my PhD at the moment (caused by AIRE gene deficiency). I’m definitely not an expert, but I don’t think it’s a leading theory. As always in biology, autoimmune diseases probably have dozens different causes. Many of them might be environmental or genetic. Better yet a combination of the two.

atombender17 hours ago

There's also some really compelling evidence that psoriasis is caused by bacteria. Psoriasis is often described as autoimmune, but is probably better described as immune-mediated disorder. Unlike autoimmune disorders like MS and lupus, psoriasis doesn't involve the body "attacking" itself.

Specifically, streptococcus bacteria such as Streptoccocus pyogenes, also called Group A Streptococcus, which is primarily responsible for rheumatic fever and scarlet fever in developing countries, and more commonly known in the West for causing strep throat (streptococcal pharyngitis).

We already know with almost certainty that S. pyogenes triggers a form of psoriasis called guttate, which in 60% of cases resolves on its own within 1-3 months. But in the remaining cases, it turns chronic. It can also come and go: spontaneously resolving and then coming back a few months after.

What's particular about strep is that it appears that it can lie dormant in the body. The tonsils of psoriasis sufferers have been found to contain strep bacteria, and a recent meta-study concluded that a tonsillectomy can significantly improve psoriasis in about 70% of patients who undergo the procedure; so it's likely that the tonsils act as a reservoir for continuous reactivation. (Apparently, people who have a tonsillectomy as a child are also less likely to develop psoriasis.) Strep bacteria are also thought to evade serological detection by hiding in biofilm, from which they periodically emerge to reactivate the immune response.

As to why only some people develop psoriasis, the explanation might be some kind of genetic predisposition. Psoriasis is often explained as maybe being caused by "cross talk" between the adaptive and innate immune systems.

Some papers:

Streptococcus pyogenes-induced cutaneous lymphocyte antigen-positive T cell-dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis https://pubmed.ncbi.nlm.nih.gov/27056267/

Group A streptococcal pharyngitis: Immune responses involved in bacterial clearance and GAS-associated immunopathologies https://pubmed.ncbi.nlm.nih.gov/28951419/

Psoriasis, chronic tonsillitis, and biofilms: Tonsillar pathologic findings supporting a microbial hypothesis https://pubmed.ncbi.nlm.nih.gov/29554401/

Psoriasis, chronic tonsillitis, and biofilms: Tonsillar pathologic findings supporting a microbial hypothesis https://pubmed.ncbi.nlm.nih.gov/29554401/

Tonsillectomy and the subsequent risk of psoriasis: A nationwide population-based cohort study https://pubmed.ncbi.nlm.nih.gov/33548305/

Mechanisms of microbial pathogenesis and the role of the skin microbiome in psoriasis: A review https://pubmed.ncbi.nlm.nih.gov/30981296/

jjcon22 hours ago

Any thoughts as to why autoimmune diseases are (or at least seem) more prevelent in the 1st world?

epgui21 hours ago

Broadly speaking, the hygiene hypothesis is the current leading explanation.

To make an analogy, in AI/ML terms, it amounts to a training set problem: you're not exposed to a diverse enough set of microbes and pathogens, or you're exposed to a biased sample, or you're not exposed to enough microbes.

Your immune system's role is to act as a classifier to discriminate between good and bad, self and non-self. When you have a bad training set, you increase the odds that good things will be identified as bad, or that self antigen will be recognized as foreign.

Broken_Hippo8 hours ago

If your country doesn't have a medical system that will detect such things in the general population and does not have a system to get the numbers for statistics, how are you going to know how prevalent something is?

We don't know how common lots of things are in 1st world countries either, simply because we don't track.

colechristensen21 hours ago

Four candidates: hygiene, better diagnostics, different exposures, longer safer lives.

dham17 hours ago

Parasites. When you start getting rid of parasites in 3rd world communities, auto immune issues start to crop up. It's thought that since the body isn't fighting off parasites then it sits idle and starts attacking itself. It kind of makes sense from a purely evolutionary perspective. There's actually been treatments for some auto immune diseases that involve giving a relatively harmless parasite to people.

f6v6 hours ago

They’re just probably under-diagnosed in the 3rd world.

mactournier20 hours ago

Contrary to the HN title, the paper is not about causal inference, it is a case-control study. A good primer on the limitations of case-control studies can be found here: https://www.medicalnewstoday.com/articles/280936#limitations

letmevoteplease19 hours ago

The abstract of the study states, "These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS."

axlee18 hours ago

Your contrarian approach is detrimental to proper research. Authors have found a very strong link that cannot be explained by any other risk factors. What risk factors are you suggesting they should look into?

deltaonefour22 hours ago

This is a bit off topic but I have a question about causality.

Is causality really a fuzzy concept? For example I assume if action A causes event B I assume the connection is 100%. Can we really say that action A has a 30% chance of causing event B?

I ask because the more I think about it, when someone says action A causes a 30% chance of event B occurring what he is technically saying is action A is one causative factor that must occur and that we're missing information about other causative factors.

In the case of this article. A causative link is established between EBV and MS to a fuzzy probable degree. This seems to me that technically what's actually occurring is that a fuzzy causal link simply means that there are other causative factors we don't yet know about, and likely this is a specific type of immune system that reacts to EBV in a certain way.

Would my assessment be accurate? All causal connections are either 100% and any fuzziness just means we're missing information about other joint causal events that must occur to trigger the outcome. Does anyone who's a statistician know?

dataflow20 hours ago

> Is causality really a fuzzy concept? For example I assume if action A causes event B I assume the connection is 100%. Can we really say that action A has a 30% chance of causing event B?

The world is probabilistic at the quantum level so I don't see how it could be otherwise.

> I ask because the more I think about it, when someone says action A causes a 30% chance of event B occurring what he is technically saying is action A is one causative factor that must occur and that we're missing information about other causative factors.

To my knowledge this has been physically disproven: https://en.wikipedia.org/wiki/Hidden-variable_theory#Bell's_...

(Note I'm just responding to your philosophical question, not the biological one. In particular I'm not suggesting anything about the practical relevance of quantum effects to the biology discussion here, or lack thereof.)

beaconstudios15 hours ago

this doesn't occur above the quantum level though.

peter30322 hours ago

There was a similar debate in the 1880s. Dr. Robert Koch claimed some diseases were caused by bacteria and developed a procedure to prove it. The germ theory of disease was controversial until then.

Its suspected several diseases without known causes may be caused by a bacterium, virus or protein. But lack the evidence to satisfy the Koch postulates. These diseases include some cancers and many human nervous system diseases.

sva_20 hours ago

> All causal connections are either 100% and any fuzziness just means we're missing information about other joint causal events that must occur to trigger the outcome.

I think one theory is, that the immune system has a way of approximating the surface of a protein, and in this way recognizes what to build antibodies against. This process could be a source of fuzziness as the "protein signatures" of a virus may vary from person to person. There is also the question how those signatures are stored and retrieved in the immune system, and why they -presumably- lead to the immune system misrecognizing myelin sheaths as a threat (in some people, some of the time.)

csee21 hours ago

This is more in the domain of philosophy than statistics.

I wrote something in response, but then saw that the Wiki article on causality was far better than what I wrote, so have a look at that.

https://en.wikipedia.org/wiki/Causality

https://en.wikipedia.org/wiki/Necessity_and_sufficiency

gwern21 hours ago

Is it helpful to ask about 'percentages' here? Is oxygen 0% or 100% of the cause of you posting here? What about gravity?

Whenever you have a causal question, often taking a Pearlean perspective and asking about interventions would be more useful. For example, there is an EBV vaccine being worked on right now. If you believe OP that EBV infection is a necessary but not sufficient condition for 90% of MS cases, then it would be reasonable to say something like "if we intervened by making everyone got the EBV vaccine, then there would be ~90% fewer MS cases than in the counterfactual universe where everything else was the same but no one got the EBV vaccine." That sounds much more interesting and meaningful to me than talking about how "EBV is necessary but not sufficient".

echelon22 hours ago

> we're missing information about other causative factors.

Welcome to biology.

Perhaps EBV is particularly immunogenic, but it has to reactivate in the presence of CD8+ T-cells or CD20+ B-cells along with some other self-signal or co-infection. Perhaps there's a chain of immune signaling that must happen upstream in other immune cell populations.

Perhaps other agents can trigger autoimmune behavior in these cells, and EBV isn't strictly required. Maybe other viruses in the herpesvirus family (HSV, zoster, etc.) There could be more than one set of causes, and they might not even look similar.

In the crazy absurd limit, maybe nothing at all. Maybe autoimmunity sporadically arises with no causal agent. Random radiation hits the cell at the wrong time.

All or none of these could be the case. Diseases can have a multitude of causes, sometimes with complex interactions and interdependencies, sometimes not. With cancer it's a progression of increasingly worse state changes, and that could be the case here too.

beaconstudios15 hours ago

simple, 1:1 causality (if I flick a light switch, the light turns off) is not fuzzy at all. Complex causality is more complex (obviously) and most things in real life have complex causality.

aljungberg23 hours ago

The parallel to Guillan Barré Syndrome seems intuitive. MS and GBS are both autoimmune disorders which damage myelin. MS is slower and chronic while GBS is acute and rarely relapses. What if MS is a low grade persistent immune response to a chronic viral infection such that those bad antibodies are created in small amounts indefinitely?

obert8 hours ago

Glad that we might eventually get rid of diseases from starting, but when it comes to a cure, research is unbalanced towards treating instead, because it makes more money.

scotty7912 hours ago

I wonder how many viruses infecting humans we know nothing about just because they don't cause any obvious symptoms.

clord23 hours ago

I wonder if MS is like the EBV version of shingles: if you don't get it early, when you do, it's a much worse disease. Most people pick it up early, but those who manage to avoid it and then get it late are in danger. Another instance of hygiene hypothesis.

vintermann23 hours ago

MS isn't, but yes, Epstein-Barr virus is more serious if you first catch it as an adult. That will likely knock you out with mononucleosis, a.k.a kissing sickness, for a few weeks. Fatigue can linger a lot longer.

latortuga21 hours ago

Definitely my experience. I had it as an adult at 26 and it absolutely knocked me out for weeks. I lost a ton of weight from having no appetite and having a constant sore throat. Sleeping was also terrible because I couldn't breathe easily. I think I missed 3 or 4 weeks of work and even when I started back I could only work half days for awhile at my not-strenuous desk job.

sabujp23 hours ago

I was wondering what the genetic factors are that cause EBV to push people to get MS and found this excellent paper [1] (see the genetic susceptibility section).

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334604/

[2] https://www.google.com/search?q=genetic+factors+that+cause+E...

onemoresoop22 hours ago

Interestingly, Moderna has some trial for mRna vaccine for Epstein-Barr virus [0]

[0]- https://www.clinicaltrialsarena.com/news/moderna-ebv-vaccine...

cjensen20 hours ago

It's weird to me that they say 35 of the 801 MS cases were negative then positive before getting MS. The control group had 107 of 1566 were negative, but they don't bother to tell us how many of them ended up positive.

I assume enlisting is a high-risk place to get EBV, and without info on the control I don't see how you can draw conclusions. But I'm basing this on the summary rather than the actual article: does the article have the info?

couchand17 hours ago

It's well known that (1) most people have EBV some time in their life, and (2) most people don't have MS. The news that any number of people who don't develop MS get EBV would be mundane.

xdrone21 hours ago

Here's a John McDougall talk, he had some close ties to Dr Swank, known for a lot of early MS research.

https://www.youtube.com/watch?v=fmZdI8jinIw

tldw: When your stomach layer is compromised, unprocessed food gets into your body. Food like animal protein, similar to our proteins, get attacked by the immune system, some of your cells are also mistakenly attacked.

Anyone with the compromised stomach is at greater risk for auto immune diseases. For example look of rates of ms among celiac or crohn's sufferers.

Same goes for type 1 diabetics, also autoimmune. Research suggests casein from dairy gets in the body, your immune system accidentally attacks your pancreas insulin making cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518798/

sumosudo21 hours ago

All the health problems of modern society can be diminished greatly by ensuring the proper functioning of the gut.

bagacrap14 hours ago

please tell me how to ensure proper function of my gut

howinteresting23 hours ago

This study appears to suggest that MS is essentially "long Epstein-Barr." Terrifying if the same pattern holds for covid, given the number of people who have some sequelae (the most conservative estimates are 2-5% for "serious" post-viral symptoms, which would be hundreds of millions of people worldwide). There will be an extraordinary amount of suffering, not to mention radical shifts in economic and public policy.

kmeisthax23 hours ago

There's another paper from June of last year[0] that proposed a long COVID explanation: Epstein-Barr reactivation. I haven't seen any follow-up work yet, but if both that and this paper have any predictive power to them[1] we might start seeing a cohort of "long long COVID[2]": people who got COVID, didn't recover, and then progressed to MS.

[0] https://pubmed.ncbi.nlm.nih.gov/34204243/

[1] I'm particularly worried about the "EBV reactivation" theory as COVID-related studies have been used as a vehicle for many medical frauds.

[2] As per ISO standards long long COVID must have an infection duration represented with at least a 64-bit machine integer

vintermann23 hours ago

That sounds unlikely. Epstein-Barr is a herpesvirus, and it's persistent - once you catch it, it stays latent in your body and you'll shed it through your saliva periodically for life.

As far as I can find, coronaviruses have no way to pull that trick. Once your immune system gets rid of it, it's gone and not coming back unless you're infected again by a sufficiently unrecognizable relative.

Tagbert21 hours ago

Like my uncle, Oscar? He looks nothing like anyone else in the family and looks out of place in family photos. I’m pretty sure he is antivax, too.

axg1123 hours ago

The study really doesn't suggest that. All it suggests is that EBV seropositive people are much more likely to develop MS than the seronegative minor population.

As for long COVID, the data quality is very variable. I'd like to see a controlled study that compares recovery from COVID vs. other respiratory viruses.

howinteresting22 hours ago

It's pretty clear that the causal explanation is the only reasonable one here. (Besides, at least for covid, not everyone who contracts the virus develops antibodies for it: https://journals.asm.org/doi/10.1128/Spectrum.00904-21 )

There's a reason I quoted conservative estimates of long covid. The 2% is from this ONS study: https://www.ons.gov.uk/peoplepopulationandcommunity/healthan.... The high end of estimates is 10-30%, which would mean the end of our current era of civilization.

stefan_23 hours ago

There are lots of viruses that persist forever. You can get chickenpox as a kid then die of shingles as a retiree. Measles might give you only mild symptoms then 6-15 years after reactivate and cause Subacute sclerosing panencephalitis (SSPE), a fatal brain inflammation with all the interesting symptoms that implies (starting out with mood swings progressing into dementia, muscle spasms and blindness).

Think of this the next time some brain dead person starts talking about the "unknown long term effects of the vaccine" - we know what has long term effects, and it's freaking live viruses!

f38zf5vdt23 hours ago

Coronaviruses do a weird thing where their viral RNA persists in cells long after the initial infection. [1] No one knows if this has a bearing on long COVID or not.

[1] https://www.nature.com/articles/s41592-021-01145-z

jonnycomputer23 hours ago

Yeah, I don't trust the viruses not to do sneaky shit. Not at all.

vintermann22 hours ago

It's not a terribly weird thing for a virus to do, but as far as I know (just an interested amateur) coronaviruses can't use this to stay latent.

howinteresting21 hours ago

I would be hesitant to generalize from existing coronaviruses to SARS-2. As the sibling comment points out, SARS-2 has been shown to persist in every organ of the body well after initial infection.

f38zf5vdt22 hours ago

We don't really know. A recent manuscript submitted to Nature shows minute persistence in various tissues as long as 230 days or more post-infection. [1] RNA is fragile, if the infection is completely cleared or not integrated into the genome in some way we would not expect it to persist.

[1] https://assets.researchsquare.com/files/rs-1139035/v1_covere... (Figure 1)

aserdf23 hours ago

there is an experimental[0] treatment for MS, the "immune system reboot". i am a layperson but my understanding is stem cells are taken from the patient, the immune system is "destroyed" through immunosuppressants and the stem cells are then used to rebuild a "naive" immune system in the patient.

based on the info in the OP, i wonder if the MS result from EBV is random; what is the probability of a rebooted immune system to follow the same path after exposure?

[0] - https://www.nih.gov/news-events/nih-research-matters/immune-...

wswope23 hours ago

The initial susceptibility is mostly going to be predetermined by the MHC, and therefore remain the mostly the same. However, the pathological outcome is ostensibly a product of certain strains of pathogens plus luck of the draw on somatic hypermutation in response to said pathogen.

whatshisface23 hours ago

For something as rare as MS, "spin again" is ninety percent of a cure.

wtetzner23 hours ago

An interesting talk about someone who was able to reverse a lot of her MS symptoms with a change in diet: https://www.youtube.com/watch?v=KLjgBLwH3Wc

DantesKite19 hours ago

Anecdotally I’m aware of someone who was able to reverse a lot of their symptoms with high doses of Vitamin D.

There’s a biochemist here giving advice about being cautious. That goes without saying, but it always strikes me as disingenuous careerism to recommend people with terrible illnesses to not experiment. That’s the bedrock of scientific inquiry.

It may be the case there’s nothing out there that can help alleviate MS even a little, but it’s worth trying, especially if the cost is low and the burden of the disease is high.

Broken_Hippo3 hours ago

There’s a biochemist here giving advice about being cautious. That goes without saying, but it always strikes me as disingenuous careerism to recommend people with terrible illnesses to not experiment. That’s the bedrock of scientific inquiry.

It isn't a bedrock of scientific inquiry if you aren't actually studying things. In fact, with MS it can make you so much worse off than you would be. People start the diets as a substitute for proven medicine. No diet has been proven to prevent a relapse, lessen their impact, nor cause you to have fewer relapse. With MS, every relapse you have increases your chances of disability and most relapses leaves effects. I lost hand strength and my fingertips have different feeling, for example, even though most of the numbness went away. Proven medicine has lessened the number of relapses folks have and often makes them milder: With the best medicine, we haven't prevented relapses entirely - though a lot of neurologists treat a single relapse as a sign to switch medications to something that'll work better for you.

I'll add that it isn't always worth trying. You aren't doing science unless you are part of a trial. Eating a strict diet isn't generally cheaper and takes time that you might not even have the energy for - all for something science hasn't been able to prove works. Just ancedotal stuff from random people without anything to back it up. I suspect the diet might just have a similar effect that weed does with spasticity: It doesn't medically cure some it, but people report being less bothered by them. And if that's the case, any dietary change would work and you probably shouldn't give money to the ones claiming miracles.

garganzol5 hours ago

I confirm the effects of vitamin D3 with my own observations.

Vitamin D3 is an adaptogen for the immune system, it is an antioxidant in mitochondria, it plays so many different roles.

No wonder it has such a beneficial effect on MS and CFS/ME patients who suffer from autoimmunity and mitochondrial manifestations. Vitamin D3 alone is not the ultimate cure per se, but it is a part of a possible cure for sure.

Note of caution to those who supplement vitamin D3 for more than 2 months: always add vitamin K2 MK-7 to the mix to avoid the possible development of arterial calcification.

Broken_Hippo8 hours ago

The Wahls protocol is a scam. It is not a cure for MS.

Most folks with MS have RRMS - RR stands for relapsing remitting. Basically, you have a "flare" - when your body attacks your nerves. You have symptoms for a while, and then they start to go away. For context: I woke up one morning half blind. I could tell if there was a red object, but I couldn't make out what it was. Everything I could see out of my left eye was fuzzy. I couldn't make out the big "E" on the eye chart.

But then, the lesion heals. You might be left with some damage, but a lot of it goes away. My vision returned and the optic nerve healed well. My vision is actually better in that eye than the other one. I have lingering numbness in my hands from time to time, but nothing like the fingertip-to-elbow pins and needles from a flare (I barely notice).

All this means that a change in diet might seem to make your MS better. It definitely makes folks feel like they have control. But clinically, it does nothing. You are taking a big risk by doing this. What does work are modern DMTs - disease modifying treatments.

garganzol4 hours ago

It is not a scam. As you said, it is just not the ultimate treatment for MS. But it is a tool for MS management.

Protocols like this are important parts of treatment for many people with similar conditions: T2DM, neuropathy, CFS/ME, Alzheimer, Parkinson, POTS.

I want to stress that many people with conditions adjacent to MS do not experience that relapsing-remitting nature of a disease. And they confirm an immediate improvement when they swap junk processed foods with more natural choices.

epgui21 hours ago

Biochemist here: I would advise to exercise strong caution when looking at dietary changes in the context of MS.

A lot of advice gives people the illusion that they have more control over their illness than they actually do, and a lot of the diets cause unnecessary harm (as a heuristic: the more things you cut out, the higher the potential for harm).

That said, healthy eating and regular physical exercise is always a good idea, and even more so if you have any existing illness.

Broken_Hippo8 hours ago

Thank you!

A lot of scam diets promise to cure MS. Books are sold. But the only real way to lessen the harm of the disease is through a combination of a modern medicine and luck (I've had both).

Agree on the general healthy eating and activity, though.

garganzol19 hours ago

According to numerous observations, neurodegenerative diseases and the lack of energy (adenosine triphosphate, ATP) are tightly interconnected.

Thanks for posting. And yes, there is mitochondria involved, once again.

moneywoes23 hours ago

So basically no wheat, milk and processed foods?

omreaderhn23 hours ago

I skimmed through the presentation and I'm not sure how you arrived at that as your takeaway. The dietary advice given in there is much more complex than that.

mirekrusin23 hours ago

Is anybody testing for virus/bacteria vs virus/bacteria interactions?

kisamoto20 hours ago

I will read this but as someone who has had a family member diagnosed with MS if there are other connections or papers people can recommend I would be very grateful.

gregwebs16 hours ago

Dr. Terry Walhs was diagnosed with MS and became wheel chair bound. She came up with a protocol that was able to reverse her MS. I recall from previous interviews that her theory was that MS was a disease of the mitochondria. https://terrywahls.com/

Broken_Hippo8 hours ago

the Walhs protocol is generally recognized as a scam. Diet does not cure MS. If it did, diet would be first line treatment as it would be much cheaper to simply pay for someone's food than the most effective MS treatments we have. Those treatments are solely responsible for the increase in an MS patient's quality of life (over time) because they actually prevent some damage. Some, not all - they are not a cure.

And FWIW: It isn't uncommon for someone with MS to use a wheelchair temporarily. OR a cane. I was half blind for 6 weeks, but that went away years ago. I spent time with numb hands, which has mostly (but not totally) gone away. If my legs had been affected - you guessed it, I might have used a wheelchair for a bit. All of this means that it can seem like a "cure" works when it is really just the way the disease course goes for lots of folks.

gregwebs7 hours ago

It doesn’t seem like you have spent any time understanding Dr Wahls information. It took her six years to be able to ride a bicycle.

I don’t know anyone with MS whose disease course went to effectively cured years, but I admit to being ignorant on the subject.

Broken_Hippo4 hours ago

I don't need to do that personally. If the professionals can't replicate results, then it is a sham [1]. They are selling snake oil and books full of promise they can't back up. She doesn't tend to mention that she had chemo, which you probably understand wipes out the immune system. It isn't uncommon to have little disease activity after that. You probably also don't realize that she didn't use a wheelchair because she couldn't walk, but because of fatigue. Fatigue and balance issues are really common in MS: It'd easily keep you off of a bicycle. There are medicines that help fatigue and sometimes this does ease even if you've had MS for years. There is also a good deal of overlap with depression/mood disorders and MS - which you might understand can come with their own fatigue.

And when I speak of fatigue, I'm speaking of "Oops, I showered today and I can't do anything else" sort of disabling fatigue.

Diet is not a cure for MS, and we should really quit pushing sham cures from folks preying on other people's feelings of hopelessness. Which, as you can imagine, is pretty common with MS. The most horrifying part of this is that it keeps folks from trying things that actually are proven to improve quality of life in the long run: MEdications. Medications actually prevent relapses. Diet does not.

At most, diet is important in the same way it is important for everyone else: Most folks have slightly better outcomes if they, in general, eat healthy and are active. This isn't special to MS nor do you need to follow some strict diet.

[1] https://en.wikipedia.org/wiki/Terry_Wahls

+1
gregwebs3 hours ago
_qua13 hours ago

And what's the theory for why supposedly successful treatment is not embraced by the medical community? Is it not more likely that her diagnosis was incorrect, or her course was atypical than that she independently discovered a cure which is rejected by the medical community at large?

Broken_Hippo8 hours ago

In many circles, the Wahl's protocol (basically diet) is considered a scam. Diet does not cure MS. Governments and health insurances surely would rather pay for food every month than pay the costs of current medications.

On the other hand, medications have greatly improved quality of life for MS patients over the last 20 years or so. Folks diagnosed today aren't in the same dire boat as someone 30 years ago.

gregwebs7 hours ago

As a counterpoint example someone close to me was diagnosed with irritable bowel syndrome and told by doctors that there was no treatment and that diet did not help. When she adopted a paleo like diet with no other changes the IBD symptoms went away permanently almost immediately. Another counterpoint is that I was told by doctors when I was younger that diet was not a treatment for acne. This advice being based entirely on a single study with a single dietary intervention.

I think you have a mistaken understanding of what it takes to change one’s diet. A government handout wouldn’t help in the slightest. It also doesn’t help for a doctor to give someone a list of foods to eat or not eat.

Broken_Hippo5 hours ago

Diet is not a cure for MS. Period.

A single diet might not be a cure for IBS, but IBS affects a digestive organ. Obviously, what you eat is going to affect a digestive organ, regardless of disease, and it seems obvious that a few folks have trigger foods.

And honestly, if diet were an easy way to cure acne, it'd be prescribed more. Just because you got one thing as a youth doesn't make the opposite true.

gregwebs7 hours ago

I don’t think our medical system has any mechanism to achieve high compliance for major dietary changes, so it’s very difficult to study. Drugs are very easy to study.

It’s still an N of 1 case report from a medical evidence point of view so not likely to be widely applicable.

asdfasgasdgasdg20 hours ago

Moderna are trialing an EBV vaccine. If it's successful, I wonder if we will see an end to MS. A cure would be great but failing that a prevention is almost as good.

dmitryminkovsky22 hours ago

> and the team identified 1566 matched controls for them.

Can anyone please shed some light on this? How would this work?

NerdyNumbersGuy23 hours ago

This featured quite heavily in todays issue of The RECC’E I put out this morning! Worth a quick read if you like quick- fact insights https://email.recce.news/a7i9l9x8y1

Metacelsus21 hours ago

For more on EBV, I've discussed it on my blog here: https://denovo.substack.com/p/epstein-barr-virus-more-maladi...

(It doesn't just cause MS!)

holidayacct15 hours ago
deltaonefour23 hours ago

If MS is a faulty immune response from EBV, wouldn't a vaccine theoretically and potentially trigger this same faulty immune response?

There are obviously other causative factors influencing MS. One is EBV, the other is likely a specific type of immune system.

vintermann23 hours ago

Climate is also a known factor. MS is more prevalent in temperate climates. A study from some years back suggested that if you move before the age of 15 or so, you get the risk of your new climate instead.

epgui21 hours ago

Short answer is no.

Long answer is that the question is premature (we need to answer more mechanistic questions first, and then we need to have an actual potential vaccine strategy to talk about) and there is currently no particular reason to suspect this.

adnmcq99917 hours ago

That’s why I won’t MRNA

croes23 hours ago

EBV stays in the human body, a vaccine wouldn't.

deltaonefour22 hours ago

The immune system upon reacting to EBV or a vaccine should theoretically eliminate EBV on contact so it won't stay in your body?

Are you implying that that a vaccine cannot eliminate EBV?

Additionally, a faulty immune response also means your immune system can't differentiate between EBV and your nerve cells. So theoretically speaking even if there's no EBV in your body having MS means that your body thinks EBV is in your body even if it's not. A vaccine in my mind could still induce this reaction.

croes3 hours ago

I meant that it's unlikely that a EBV vaccine triggers the same response as EBV because EBV stays and the vaccine wouldn't.

Same with the Corona vaccines unlike this implies https://news.ycombinator.com/item?id=29942670

Metacelsus21 hours ago

Some vaccines (like VZV vaccine) persist in the body.

panabee9 hours ago

are you on twitter?

your blog is highly educational. i'm interested in learning more about EBV and other viruses.

for instance, given that VZV is common but not every infection causes shingles, how does VZV pass koch's postulates to establish causality?

similar question applies to SARS-CoV-2 and CRS.

animanoir19 hours ago

I wish I was still a virgin.

cheaprentalyeti24 hours ago

I saw this news item last night, posted next to that one...

"Study finds hydroxychloroquine delays disability for least treatable form of multiple sclerosis" [0]

[0]: https://medicalxpress.com/news/2022-01-hydroxychloroquine-di...

xadhominemx24 hours ago

Probably not

degosuke24 hours ago

The link returns 404.

cheaprentalyeti23 hours ago
pkaye23 hours ago