[HN Gopher] Multiple Sclerosis Causality
___________________________________________________________________
Multiple Sclerosis Causality
Author : nabla9
Score : 346 points
Date : 2022-01-14 17:31 UTC (5 hours ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| mirekrusin wrote:
| Is anybody testing for virus/bacteria vs virus/bacteria
| interactions?
| sonicggg wrote:
| 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?
| killjoywashere wrote:
| 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.
| jessriedel wrote:
| 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.
| Metacelsus wrote:
| 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...
| jessriedel wrote:
| 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.
| sonicggg wrote:
| Vaccine is no guarantee though, just look at Covid. DW was
| recently covering breakthrough cases that led to Long Covid.
| You're speculating now.
| boondaburrah wrote:
| 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.
| Metacelsus wrote:
| Yeah, but will the vaccines be effective? EBV is amazingly
| good at immune evasion. Prior antibodies don't protect
| against re-infection.
| Miner49er wrote:
| 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
| jjcon wrote:
| Any thoughts as to why autoimmune diseases are (or at least
| seem) more prevelent in the 1st world?
| epgui wrote:
| 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.
| colechristensen wrote:
| Four candidates: hygiene, better diagnostics, different
| exposures, longer safer lives.
| f6v wrote:
| 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.
| deltaonefour wrote:
| 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.
| croes wrote:
| EBV stays in the human body, a vaccine wouldn't.
| Metacelsus wrote:
| Some vaccines (like VZV vaccine) persist in the body.
| deltaonefour wrote:
| 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.
| vintermann wrote:
| 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.
| epgui wrote:
| 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.
| kisamoto wrote:
| 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.
| NerdyNumbersGuy wrote:
| mactournier wrote:
| 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
| letmevoteplease wrote:
| 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."
| Metacelsus wrote:
| 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!)
| brechmos wrote:
| 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.
| cheaprentalyeti wrote:
| 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...
| xadhominemx wrote:
| Probably not
| degosuke wrote:
| The link returns 404.
| pkaye wrote:
| The link was missing the final "l".
|
| https://medicalxpress.com/news/2022-01-hydroxychloroquine-
| di...
| cheaprentalyeti wrote:
| Ah, a typo, an 'l' was missing.
|
| https://medicalxpress.com/news/2022-01-hydroxychloroquine-
| di...
| [deleted]
| clord wrote:
| 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.
| wahern wrote:
| Some have suggested that CMV (another ubiquitous herpes virus)
| induced evolutionary pressure for kissing and even monogamy:
| "Kissing as an evolutionary adaptation to protect against Human
| Cytomegalovirus-like teratogenesis",
| https://pubmed.ncbi.nlm.nih.gov/19828260/
| vintermann wrote:
| 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.
| latortuga wrote:
| 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.
| deltaonefour wrote:
| 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?
| csee wrote:
| 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
| dataflow wrote:
| > 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.)
| echelon wrote:
| > 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.
| sva_ wrote:
| > 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.)
| gwern wrote:
| 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".
| peter303 wrote:
| 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.
| Mezzie wrote:
| 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.
| jessriedel wrote:
| > 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.)
| roganartu wrote:
| > 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.
| xdrone wrote:
| 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/
| sumosudo wrote:
| All the health problems of modern society can be diminished
| greatly by ensuring the proper functioning of the gut.
| howinteresting wrote:
| 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.
| axg11 wrote:
| 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.
| howinteresting wrote:
| 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.
| vintermann wrote:
| 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.
| Tagbert wrote:
| 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.
| kmeisthax wrote:
| 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
| stefan_ wrote:
| 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!
| f38zf5vdt wrote:
| 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
| jonnycomputer wrote:
| Yeah, I don't trust the viruses not to do sneaky shit. Not at
| all.
| vintermann wrote:
| 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.
| f38zf5vdt wrote:
| 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_c
| overe... (Figure 1)
| howinteresting wrote:
| 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.
| dm319 wrote:
| 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
| jonnycomputer wrote:
| 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...
| dm319 wrote:
| Yes that's a good point.
| moneywoes wrote:
| 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
| mpreda wrote:
| [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").
| dm319 wrote:
| 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.
| dekhn wrote:
| 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.
| dm319 wrote:
| 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
| dekhn wrote:
| 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_monitor wrote:
| 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
| mdswanson wrote:
| 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://ww
| w.amazon.com/dp/B08XTNHRR5/ref=cm_sw_em_r_mt_dp_FX...
| whatshisface wrote:
| What's the connection to information theory?
| dekhn wrote:
| sorry, I shouldn't have thrown that in there.
| aserdf wrote:
| 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-...
| wswope wrote:
| 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.
| whatshisface wrote:
| For something as rare as MS, "spin again" is ninety percent
| of a cure.
| sabujp wrote:
| 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...
| wtetzner wrote:
| 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
| moneywoes wrote:
| So basically no wheat, milk and processed foods?
| omreaderhn wrote:
| 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.
| epgui wrote:
| 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.
| garganzol wrote:
| According to numerous observations, neurodegenerative diseases
| and the lack of energy (ATP) are tightly interconnected.
|
| Thanks for posting. And yes, there is mitochondria involved,
| once again.
| dmitryminkovsky wrote:
| > and the team identified 1566 matched controls for them.
|
| Can anyone please shed some light on this? How would this work?
| onemoresoop wrote:
| Interestingly, Moderna has some trial for mRna vaccine for
| Epstein-Barr virus [0]
|
| [0]- https://www.clinicaltrialsarena.com/news/moderna-ebv-
| vaccine...
| cjensen wrote:
| 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?
| asdfasgasdgasdg wrote:
| 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.
| reedf1 wrote:
| 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!
| danuker wrote:
| > 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.
| BobbyJo wrote:
| 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?
| andi999 wrote:
| If you knew you were negative yes, if the status was
| unknown then not.
| shadowgovt wrote:
| 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.
| bigbillheck wrote:
| There's the anelloviruses which are at least as prevalent and
| nobody really knows what they do.
| axg11 wrote:
| Great question. A related question: how many undiscovered
| viruses exist that are beneficial to the host?
| arbuge wrote:
| 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-Barre 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."
| jka wrote:
| 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.
| jonnycomputer wrote:
| 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?
| jka wrote:
| You could be onto something there, yep.
| jonnycomputer wrote:
| Communication is hard.
| zepto wrote:
| It is, but there are some easy heuristics before you get
| to the hard stuff.
|
| One is that telling people how they should feel about
| things is usually irritating.
| jka wrote:
| It certainly is.
|
| Here's a (probably totally unrelated) comment that I
| think is good food for thought:
| https://news.ycombinator.com/item?id=29917158
| jonnycomputer wrote:
| Interesting.
| jka wrote:
| :)
| dwmbt wrote:
| > 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.
| RspecMAuthortah wrote:
| 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.
| currency wrote:
| 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.
| rmind wrote:
| 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.
| panabee wrote:
| thanks for sharing. does this test for EBV in both latent
| and lytic phases?
| cestith wrote:
| 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.
| epgui wrote:
| 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.
| lalaland1125 wrote:
| One important thing to note is that EBV is extremely prevalent.
| Almost everyone gets it eventually and very few of those people
| develop MS.
| jonnycomputer wrote:
| But a lot of people don't really develop severe symptoms
| either, right?
| cestith wrote:
| 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.
| marvin wrote:
| 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.
| peter303 wrote:
| Possibly a co-factor, since many get EBV and few MS.
| nefitty wrote:
| 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.
| nradov wrote:
| What are the relevant interventions? Which genes correlate
| with MS?
| nefitty wrote:
| 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.
| f38zf5vdt wrote:
| 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
| config_yml wrote:
| Interesting. My sister and I both had mononucleosis before
| puberty, and she was diagnosed with MS in her late twenties.
| [deleted]
| [deleted]
| cjensen wrote:
| 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.
| MaximumYComb wrote:
| 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.
| Severian wrote:
| Found this in my news feed, so this timely. Good news I guess!
|
| https://www.forbes.com/sites/roberthart/2022/01/14/moderna-s...
| Miner49er wrote:
| 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.
| garganzol wrote:
| 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.
| rmind wrote:
| 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/
| radicalbyte wrote:
| 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.
| garganzol wrote:
| 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
| thewebcount wrote:
| 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.
| aljungberg wrote:
| The parallel to Guillan Barre 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?
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