[HN Gopher] Scientists discover a cause of lupus, possible way t...
       ___________________________________________________________________
        
       Scientists discover a cause of lupus, possible way to reverse it
        
       Author : adamredwoods
       Score  : 735 points
       Date   : 2024-07-10 21:24 UTC (1 days ago)
        
 (HTM) web link (news.feinberg.northwestern.edu)
 (TXT) w3m dump (news.feinberg.northwestern.edu)
        
       | ipunchghosts wrote:
       | I wonder if any of these findings help us better understand
       | me/cfs.
        
         | galangalalgol wrote:
         | It has been my hope that the number of me/cfs cases would
         | finally drive enough research into autoimmune disorders in
         | general, that we might finally figure it out. It seems very
         | poorly understood from an outside perspective.
        
           | PaulKeeble wrote:
           | There is no funding and since Long Covid appeared the funding
           | for ME/CFS has completely vanished. If Long Covid ME like
           | illness is the same then ME/CFS is getting lots of research
           | right now, on the other hand if they turn out to be different
           | ME/CFS patients are getting completely ignored.
        
             | thenerdhead wrote:
             | Many ME experts are doing both. RECOVER is considering
             | adding ME/CFS arms to its huge clinical trial platform.
             | UCSF just added ME/CFS as a priority in their LIINC
             | program.
             | 
             | SARS-CoV-2 therapeutics won't work on both but immune cell
             | based ones may given they haven't been tested in either
             | yet.
             | 
             | Both suggest a root cause of persistent viral antigen. Time
             | will tell what works here.
        
               | Elinvynia wrote:
               | RECOVER is the biggest scam when it comes to research
               | unfortunately. 90% of their studies are focusing on
               | various form of "brain exercises", CBT therapy and
               | exercise therapy. Things that are not only proven to not
               | work, but actually proven to harm people with ME/CFS (of
               | which long covid patients make up a large amount).
        
               | thenerdhead wrote:
               | They fund and do a lot of work beyond the horrible
               | choices for initial RCTs. This fall we should hopefully
               | see actual pharmaceutical interventions and a plethora of
               | research they've been publishing.
               | 
               | The more important parts of their programs are the omics
               | and tissue biopsy programs.
               | 
               | May they hopefully turn the ship...
        
           | wpasc wrote:
           | For what's it's worth, autoimmune drugs are amongst the
           | highest grossing due to their cost. Rheumatoid arthritis,
           | psoriasis, MS all do have a lot of study. I wouldn't say it's
           | enough, but I don't think the prevalence of me/cfs alters
           | anything due to the high prevalence of the other diseases.
           | Immune disorders are definitely mysterious though
        
         | PaulKeeble wrote:
         | Maybe but the immune dysfunction goes further in ME/CFS its not
         | just a problem of reduced CD4 and heightened CD8 (which are the
         | two cell types they seem to be talking about) its a wider set
         | of oddities that seem related to exhausted cells with not
         | enough energy stuck in "there is infection near by" operation
         | mode. It might help reduce symptoms that are caused by the
         | imbalance so it would certainly be worth a trial when they work
         | out the details.
        
           | trhway wrote:
           | >stuck in "there is infection near by" operation mode
           | 
           | There are bunch of articles on successful treatment of CFS
           | with methotrexate (which causes B-cells depletion whereis
           | original CFS was associated in particular with B-cells over-
           | presence after say viral infections/etc.)
        
         | avgDev wrote:
         | I've encountered an individual who had fibro, me/cfs, pots
         | diagnosis. Turns out his small nerve fibers were fried by an
         | antibiotic. His skin punch biopsy showed reduced fibers. This
         | may not be the case in everyone, but SFN is extremely under
         | diagnosed.
         | 
         | He was a chemist, and he ended up healing all his symptoms with
         | pirenzepine. If I recall correctly they did the skin punch
         | biopsy again and his physician was stunned when they saw
         | regrowth of the fibers.
         | 
         | Today, WinSanTor is in stage 3 trials with their drug. They
         | designed a cream with main ingredient being pirenzepine. They
         | are targeting diabetes but the med appears to work for small
         | nerve fibers as well.
         | 
         | Small nerve fibers control so much that any time people have
         | weird unexplained symptoms it should be explored.
        
           | carynh wrote:
           | > He was a chemist, and he ended up healing all his symptoms
           | with pirenzepine.
           | 
           | As in taking it orally for his SFN? That sounds equally
           | fascinating as it sounds unlikely to me so I'd def love to
           | read a bit more about it!
        
             | sharpshadow wrote:
             | Indeed Pirenzepine[1] is a muscarinic receptor antagonists.
             | "The muscarinic receptor is a protein involved in the
             | transmission of signals through certain parts of the
             | nervous system, and muscarinic receptor antagonists work to
             | prevent this transmission from occurring."[2] I could
             | imagine that a let's say relaxed nervous system recovers
             | better.
             | 
             | 1. https://en.m.wikipedia.org/wiki/Pirenzepine 2. https://e
             | n.m.wikipedia.org/wiki/Muscarinic_receptor_antagoni...
        
             | avgDev wrote:
             | Yes, he did take an oral dose, I believe it was higher than
             | recommended dose, so some risk involved. I don't really see
             | any studies on oral administration, but the new cream
             | showed systemic relief.
        
         | treprinum wrote:
         | Isn't thiamine tissue deficiency at the bottom of dysautonomia?
         | Potentially leading to Alzheimer, MS, ALS over long periods of
         | time if untreated depending on one's genetics and the way their
         | body tries to adapt to it? I understand nobody tracks this over
         | 30 years though. I think it's low-risk to try to address long-
         | term tissue B1/B2/B3 deficiencies first and see if it helps.
         | 
         | "The initial symptoms of thiamine deficiency beriberi are those
         | of dysautonomia [1], a broad term that describes any disease or
         | malfunction of the autonomic nervous system. This includes
         | postural orthostatic tachycardia syndrome (POTS), inappropriate
         | sinus tachycardia (IST), vasovagal syncope, mitral valve
         | prolapse dysautonomia, pure autonomic failure, neurocardiogenic
         | syncope (NCS), neurally mediated hypotension (NMH), autonomic
         | instability and a number of lesser-known disorders such as
         | cerebral salt-wasting syndrome. Dysautonomia is associated with
         | Lyme disease, primary biliary cirrhosis, multiple system
         | atrophy (Shy-Drager syndrome) Ehlers-Danlos syndrome and Marfan
         | syndrome for reasons that are not fully understood [2]. It has
         | been hypothesized that the association of dysautonomia with so
         | many different diagnoses is because a common form of
         | dysautonomia originates from high calorie malnutrition. This
         | leads to loss of oxidative efficiency (pseudo hypoxia) and
         | subsequent disorganization of ANS controls that are mediated
         | through the limbic system and brainstem."
        
           | heartrending wrote:
           | Yes for some cases and any doctor who knows anything about
           | dysautonomia tests and treats for it. It's not root cause for
           | many though because dysautonomia is a syndrome with
           | potentially hundreds of reasons with the biggest being post-
           | viral (autoimmune hypothesis) and EDS (vein elasticity
           | hypotheis).
        
         | thenerdhead wrote:
         | Very likely. All of these illnesses are diseases of the cells.
         | We're entering the golden age of immune cell science. You
         | figure out what immune cells are causing disease and how to
         | restore them.
         | 
         | Here the T cells are imbalanced and a specific protein is found
         | to regulate the imbalance but the interferon is countering the
         | protein's effects. Now you can target that in many ways and run
         | all sorts of clinical trials.
        
           | eszed wrote:
           | It seems to me that as we've gone layers deeper into organic
           | processes we've repeatedly recapitulated Galenic theory:
           | "rebalancing" more and more precisely-targeted "humours". Not
           | saying this is bad - in fact, quite the contrary: it seems
           | like a necessary stage on the way to more-sophisticated
           | mechanitistic understanding.
        
       | BenFranklin100 wrote:
       | Autoimmune diseases, of which lupus is but one of many, are
       | essentially black boxes. It's proven extraordinarily difficult to
       | develop therapies in this area. As such, this is great news.
       | Hopefully this research will encourage pharmaceutical and biotech
       | companies to invest more resources into translating research
       | findings into effective therapies.
       | 
       | I haven't read the paper yet, so I can't comment on how this
       | discovery might generalize to other autoimmune diseases, but one
       | interesting bit about autoimmune diseases is that they tend to
       | run in packs. This is suggestive there may be underlying
       | mechanisms that are shared across autoimmune diseases.
        
         | atombender wrote:
         | The aryl hydrocarbon receptor (AhR), which is key to this
         | discovery, appears to be super relevant to psoriasis, another
         | autoimmune disease.
         | 
         | AhR has been known for a long time, but it seems it's been
         | somewhat mysterious until a series of recent breakthroughs. In
         | 2022, an AhR inhibitor called tapinarof, sold as VTAMA, was
         | launched, and has shown itself to be one of the most effective
         | treatments for psoriasis to date. It's also unique in that it
         | appears to have the ability to bring lasting remission. In the
         | main clinical trial, patients who used VTAMA for one year and
         | then stopped had a mean remission duration of 4 months until
         | their psoriasis returned. That is unheard of for any topical
         | medication used on psoriasis.
         | 
         | Blocking AhR has also shown promise in treating MS [1].
         | 
         | I haven't read the lupus paper, but often with papers like
         | these, the "cause" turns out not to be the actual origin, but
         | some cytokine or other protein that is more disease-specific
         | than current drug targets. This lupus discovery appears to
         | identify an imbalance that may be compensated for, but we still
         | don't know what triggers the imbalance in the first place.
         | 
         | In some cases diseases turn out to be a genetic fault, but my
         | money is on pathogens acting as the initial triggering event,
         | which then spins the immune system into a vicious cycle of
         | autoimmunity. In psoriasis we see this with strep bacteria, for
         | example, but the exact mechanisms are not well understood.
         | However, the mechanism that makes psoriasis chronic _has_ been
         | identified, a type of T-cell called a tissue-resident memory
         | (TRM) T-cell. This type of cell acts as a kind of biological
         | memory for infections.
         | 
         | [1] https://newsroom.uvahealth.com/2023/02/15/multiple-
         | sclerosis...
        
           | BenFranklin100 wrote:
           | Great comment, thanks. I'm looking forward to reading the
           | paper.
        
           | A_D_E_P_T wrote:
           | Good post. One small correction: Tapinarof isn't an AhR
           | inhibitor, it's an AhR activator, an agonist.
           | 
           | Interestingly, tapinarof is a natural product -- a sort of
           | bacterially-modified stilbene, a chemical cousin of
           | resveratrol and pterostilbene -- and several other natural
           | products also activate AhR. (Though perhaps not exactly in
           | the same way.) The most potent and readily available of these
           | is probably 3,3'-diindolylmethane.
        
             | atombender wrote:
             | Ah, thanks. I assumed tapinarof was an inhibitor, as the
             | papers on its mechanism describe it as downregulating
             | cytokines. It appears the exact mechanism isn't quite
             | clear. Bissonette et al 2021 [1]:                 Tapinarof
             | was found to bind directly to AhR, resulting in
             | downregulation of inflammatory cytokines, regulation of
             | skin barrier protein expression, and antioxidant activity
             | ... In a T-cell polarization assay, tapinarof markedly
             | inhibited T-cell expansion and Th17-cell differentiation
             | and reduced the production of IL-17, while also reducing
             | IL-17A and IL17F levels in a CD4 T-cell assay.
             | 
             | It looks like tapinarof modulates the signaling behaviour
             | of AhR, but so far the precise mechanisms are educated
             | guesses.
             | 
             | The story of tapinarof's discovery is fascinating. It's
             | produced by a bioluminescent (!) bacillus _P. luminescens_
             | that (quoting from the paper)  "lives symbiotically within
             | parasitic, soil-living entomopathogenic nematodes." It was
             | observed in the 1950s that "the nematode did not putrefy
             | once dead, in contrast to the rapid decay seen in the
             | absence of the nematode," leading to the idea that the
             | bacillus' metabolites had antimicrobial activity -- which
             | turned out to include what is now synthesized as tapinarof.
             | 
             | Coal tar is another semi-natural substance that is thought
             | to act on AhR.
             | 
             | [1] https://www.jaad.org/action/showPdf?pii=S0190-9622%2820
             | %2932...
        
               | A_D_E_P_T wrote:
               | This open-access paper is pretty interesting with respect
               | to mechanisms of action and how tapinarof differs from
               | other stilbenes and AhR agonists: https://www.jidonline.o
               | rg/article/S0022-202X(17)31543-9/full...
               | 
               | And, yeah, good point re coal tar. AhR was once thought
               | to be a toxin or junk receptor that activated liver
               | enzymes for clearance of environmental waste and other
               | chemical byproducts. The constitutive androstane receptor
               | (CAR) and pregnane X receptor (PXR) were, at one time,
               | thought to be very similar. That might still be the case
               | with respect to PXR and CAR, but I'm thinking that the
               | way to bet is that there's more to them than was once
               | thought...
        
             | Modified3019 wrote:
             | I don't have any particular point to this post, just
             | tossing out that resveratrol itself seems to be an
             | antagonist of AhR, as it seems to compete with and block
             | agonists.
             | 
             | https://onlinelibrary.wiley.com/doi/10.1155/2019/5847040
             | 
             | Also of note for those curious since I haven't seen it
             | mentioned yet, Dioxins are potent agonists of AhR.
             | 
             | My own interest in AhR is that it seems to play a role in
             | metabolism. Lower levels of exposure to AhR activators
             | seems to kick off a complicated series of effects that seem
             | to ultimately lower metabolism, potentially being a factor
             | in obesity. Higher levels of exposure to dioxins however
             | results in wasting. AhR is poster child for hideously
             | complicated biochemical relationships, so do be careful of
             | simple summaries of exposure/response relationships.
             | 
             | I would be cautious of AhR agonists though, I recall coming
             | across a number of potential negative associations in
             | regards to cardiovascular health.
        
           | reissbaker wrote:
           | AhR also appears to be significant in (mouse models of)
           | rosacea, which is another chronic inflammatory disease:
           | https://pubmed.ncbi.nlm.nih.gov/35926563/
        
           | Centigonal wrote:
           | If this approach touches Psoriasis and MS, there's a chance
           | it'll be effective for IBDs too. That would be huge.
        
           | ww520 wrote:
           | Great info. Looks like the field has advanced tremendously.
        
           | zeagle wrote:
           | This is a great response. I tapped out something longer about
           | not being as particularly impressed with the paper and the
           | headline here on HN, but as an rheumatologist just wanted to
           | say your last two paragraphs well said.
        
             | maximz wrote:
             | Hi @zeagle, sorry to hijack the thread (didn't see a way to
             | DM you)
             | 
             | I'm a PhD student working on a new lupus diagnostic blood
             | test approach [1]. Hoping to steer the project towards true
             | clinical needs.
             | 
             | I'd love to ask for your feedback as a technologist +
             | rheumatologist on a few lupus + RA diagnostic directions
             | we're considering. Would they actually be useful in your
             | practice?
             | 
             | Would you be open to a quick chat? My email is
             | maximz@stanford.edu.
             | 
             | Many thanks!
             | 
             | [1]
             | https://www.biorxiv.org/content/10.1101/2022.04.26.489314v5
        
           | dg08 wrote:
           | Thanks for posting this. My doc just prescribed vtama for me
           | a month ago and my psoriasis was gone in less than a week. I
           | didn't even finish the sample tube he gave me. Far more
           | effective than the steroid topical cream I was using before.
           | I had no idea what vtama was until reading your post.
        
             | atombender wrote:
             | Yep. The nice thing about VTAMA is that it can be used
             | continuously, unlike steroid creams. And it's unique among
             | current topical meds in that it can provide sustained
             | remission.
             | 
             | It may be that VTAMA reduces TRM cells in the skin, which
             | are the T-cells responsible for relapse. There's is an
             | ongoing clinical trial right now called KNOCKOUT [1] that
             | gives patients a "megadose" of Skyrizi, an IL-23 inhibitor
             | that has, like VTAMA, been shown to reduce TRM cells. The
             | idea is that a single huge dose could effectively cure
             | psoriasis, or at least suppress it for a very long time.
             | The results so far show that 83% of patients achieved
             | complete clearance after six months, which was sustained
             | throughout the trial period. I'm confident it will be a
             | game changer. Here [2] is an interview with the main
             | researcher.
             | 
             | Among new psoriasis drugs, there is also Zoryve, a PDE4
             | inhibitor (same mechanism as Otezla) as a cream or foam,
             | which has a different mechanism of action.
             | 
             | [1] https://www.hcplive.com/view/risankizumab-dose-clears-
             | psoria...
             | 
             | [2] https://www.hcplive.com/view/rizankizumab-knockout-
             | study-and...
        
         | kylehotchkiss wrote:
         | I have a good feeling we're going to make a fairly big impact
         | on cancer in our lifetimes with mRNA and other new discoveries
         | in our lifetime. Autoimmune issues I'm feeling much less
         | confident about. It seems like so many of the therapies are
         | "turn down the immune system". I wish there was wider study
         | into autoimmune derived mental health complications too. Maybe
         | I'm totally wrong on this (and I'm very OK to be proven wrong)
         | but maybe there's something to find here.
        
           | roywiggins wrote:
           | There is evidence that inflammation is among the causes of
           | depression:
           | 
           | https://wapo.st/3xHLze1
           | 
           | > pro-inflammatory drugs can induce people to become
           | depressed, which suggests a causative link. In one seminal
           | study published in the New England Journal of Medicine,
           | Miller and his colleagues conducted a double-blind study of
           | 40 cancer patients undergoing treatment with interferon-
           | alpha, an inflammatory cytokine.
           | 
           | > Though none of the patients had depression to begin with,
           | the inflammatory agent had a striking effect: Many became
           | depressed, a finding that has been consistently replicated.
        
             | Aerroon wrote:
             | Is this why something like vitamin C can help with
             | depression?
        
               | theGnuMe wrote:
               | What the mechanism?
        
               | sharpshadow wrote:
               | ,,Vitamin C supplementation attenuates the oxidative
               | stress (lipid peroxidation) and inflammatory response
               | (IL-6) to a single bout of exercise."[1]
               | 
               | Vitamin C is essential and gets consumed by the body and
               | needs to be replenished. For example during sickness the
               | Vitamin C consumption is higher which could lead quickly
               | to low levels.
               | 
               | 1. https://pubmed.ncbi.nlm.nih.gov/32162041/
        
               | lyall wrote:
               | I don't believe there is any evidence that vitamin C
               | reduces inflammation or helps with depression. Vitamin C
               | is an antioxidant, not an anti-inflammatory agent.
               | 
               | There is evidence that things that reduce systemic
               | inflammation help with depression. Fish oil, or more
               | generally a balanced omega-3/omega-6 intake is one
               | example. Curcumin is another. However the effects are
               | modest, which is probably to be expected with a condition
               | as diverse as depression.
        
             | funnym0nk3y wrote:
             | However the causality is not clear. Inflammatory agents
             | cause depression. And most depressed people have higher
             | pro-inflammatory markers. It could also be the case that
             | the inflammation is a result of something completely
             | different.
        
           | steelframe wrote:
           | > Autoimmune issues I'm feeling much less confident about. It
           | seems like so many of the therapies are "turn down the immune
           | system".
           | 
           | The immune system has many branches, and you can effectively
           | deplete one branch of the immune system while preserving the
           | other branches to fight infection. For example with MS a very
           | effective treatment is CD20+ B cell suppression, as rituximab
           | does. For many people diagnosed with MS this has been
           | effectively a "cure," in the sense that while they need to
           | continually deplete their CD20+ B cells, their disease
           | doesn't progress in any meaningful way, and their immune
           | systems remain largely able to fight infection.
           | 
           | So we don't need to wholesale "turn down" the entire immune
           | system for many autoimmune diseases. Rather, we need to
           | surgically target specific parts of it and either suppress
           | those parts or modify their behavior. Given the success we've
           | seen with ritixumab and MS I'm more optimistic about our
           | prospects for finding effective treatments for autoimmune
           | conditions.
        
             | hanniabu wrote:
             | And all of this is controlled by your microbiome which is
             | always ignored. I really wish more money was put towards
             | researching that. It's literally our body's bioreactor.
        
               | phito wrote:
               | Is it really controlled by the microbiome or is it just a
               | factor among many others?
        
               | meindnoch wrote:
               | Ah yes, the "gut" meme.
               | 
               | No, the immune system is not controlled by our
               | microbiome. The microbiome interacts with, and modulates
               | the immune system in various ways, but it's hardly
               | "controlling" it. There are germ-free animal models with
               | sterile guts, which demonstrate that you can live without
               | a microbiome - of course not 100% healthy, but they can
               | still live and reproduce.
               | 
               | The immune system is modulated by a lot of things:
               | circadian rhythm, environmental stress, nutrients, etc.
               | Yes, the gut microbiome is one of them. But let's be a
               | bit more nuanced than Joe Rogan or The Liver King.
        
           | MR_Bulldops wrote:
           | I am here to restore your confidence about autoimmune issues.
           | 
           | Recently (and still in many cases) "turn down the immune
           | system" was the treatment for most cancers. Of course, the
           | purpose of anti-cancer drugs isn't to turn down the immune
           | system. It just happens that the side effect of drugs that
           | target cancer cells also target other rapidly-dividing cells
           | like hair, endothelial, and immune cells.
           | 
           | In fact, chemotherapy drugs like Methotrexate are prescribed
           | - at lower doses than for cancer patients - to people with
           | Lupus and other autoimmune diseases.
           | 
           | There are similar challenges with cancer and autoimmune
           | diseases, so progress in one might help progress in the
           | other.
           | 
           | From the article: "They are now working to find ways to
           | deliver these molecules safely and effectively to people."
           | This is a challenge for many potentially effective cancer
           | treatments as well.
        
             | spondylosaurus wrote:
             | And some autoimmune treatments started out as failed
             | attempts at developing cancer treatments, too. Happy
             | accidents!
        
               | kylehotchkiss wrote:
               | I <3 all the happy accidents that allow us to live much
               | healthier and longer lives than the generations before us
        
             | idunnoman1222 wrote:
             | Killing quickly dividing cells as a way of modulating
             | immune system is 'turn down the immune system'
             | 
             | Just as antivirals are actually 'stop cell division'
             | 
             | Neither of which inspire any confidence
        
               | MR_Bulldops wrote:
               | It should inspire confidence that we have moved beyond
               | that for many types of cancer. And if it can be done with
               | cancer treatment, we are closer to doing it with
               | autoimmune and anti-virus treatments.
        
         | fnord77 wrote:
         | > Autoimmune diseases, of which lupus is but one of many, are
         | essentially black boxes.
         | 
         | Hardly. Treatments are down to the kinase level these days,
         | which is just one step away from the gene transcription
         | factors.
         | 
         | In fact it is pretty amazing how well understood the complex
         | mechanism of autoimmune diseases are.
        
         | _glass wrote:
         | Yes, for Hashimoto's thyroiditis there seem to be some
         | approaches: https://pubmed.ncbi.nlm.nih.gov/38621508/ Let's see
         | how this plays out.
        
       | trhway wrote:
       | On one side we have in this article :
       | 
       | " insufficient activation of a pathway controlled by the aryl
       | hydrocarbon receptor (AHR), which regulates cells' response to
       | environmental pollutants, bacteria or metabolites. Insufficient
       | activation of AHR results in too many disease-promoting immune
       | cells, called the T peripheral helper cells, that promote the
       | production of disease-causing autoantibodies.
       | 
       | To show this discovery can be leveraged for treatments, the
       | investigators returned the aryl hydrocarbon receptor-activating
       | molecules to blood samples from lupus patients. This seemed to
       | reprogram these lupus-causing cells into a cell called a Th22
       | cell that may promote wound healing from the damage caused by
       | this autoimmune disease.
       | 
       | "We found that if we either activate the AHR pathway with small
       | molecule activators or limit the pathologically excessive
       | interferon in the blood, we can reduce the number of these
       | disease-causing cells,"
       | 
       | On the other side quick search on AHR activation brings for
       | example cancer related stuff like this :
       | 
       | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570930/
       | 
       | "AHR activation to promote tumor cell intrinsic malignant
       | properties and to suppress anti-tumor immune responses [14],
       | [17], [18]. Specifically, the AHR drives cancer cell migration,
       | invasion, and survival, regulates cell cycle progression and
       | promotes cancer stem cell characteristics [14], [19], [20], [21],
       | [22]. Simultaneously, it inhibits anti-tumor immunity "
       | 
       | Human body by its complexity and our lack of understanding of it
       | sometimes reminds the codebases i've worked on :)
       | 
       | In that rabbit hole of articles on AHR there is also :
       | 
       | https://www.nature.com/articles/s41423-020-00585-5
       | 
       | "The aryl hydrocarbon receptor and the gut-brain axis"
       | 
       | which in particular discusses what looks to me (i'm not a doctor)
       | like a connection/correlation : gut microbes -> AHR ->
       | glioblastoma.
        
         | elcritch wrote:
         | Both reactions make sense to me. Too much AHR activation
         | suppresses immune response leading to cancer proliferation due
         | immune cells not culling cancerous cells, but too little leads
         | to auto-immune conditions. It's definitely like a large sloppy
         | code base with lots of implicit overlaps and global effects.
        
           | wizzwizz4 wrote:
           | If all you have is a hysteresis, everything looks like a
           | chemical imbalance.
        
           | trhway wrote:
           | seems to be saying just that :
           | 
           | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140757/
           | 
           | "Autoimmunity and cancer as two sides of the same coin. The
           | figure depicts how tuning of immune system regulatory
           | mechanisms can contribute to autoimmunity, health, or cancer
           | development."
           | 
           | One can wonder if induction of some autoimmune condition may
           | be used as a treatment of some cancers.
        
             | worstspotgain wrote:
             | > One can wonder if induction of some autoimmune condition
             | may be used as a treatment of some cancers.
             | 
             | This is one of the bases of the checkpoint inhibitor
             | revolution in immunotherapy. [1] The checkpoint is there to
             | prevent immunity excesses. Temporarily turning it off is
             | effectively an autoimmune disorder [2], one that can take
             | out the cancer.
             | 
             | [1] https://en.wikipedia.org/wiki/Checkpoint_inhibitor
             | 
             | [2] https://www.frontiersin.org/journals/immunology/article
             | s/10....
        
               | zeagle wrote:
               | Similarly checkpoint inhibitors can cause autoimmune
               | conditions that look a lot like lupus, arthritis,
               | inflammatory bowel, endocrine disorders, etc. and it's
               | sometimes difficult to be able treat both as it can be
               | antagonistic. E.g. one of the checkpoint inhibitors has
               | the opposite effect of a drug used to treat rheumatoid
               | arthritis.
        
       | beekaywhopper wrote:
       | script writers for House are shaking in their boots
        
         | nadermx wrote:
         | "You stash your drugs in a lupus textbook?" "It's never lupus"
        
           | shepherdjerred wrote:
           | Every Time "It's Not Lupus"
           | 
           | https://youtube.com/watch?v=uXOxXnZoYGQ
        
             | adriand wrote:
             | Out of sheer boredom, I started watching this, and got as
             | far as an argument about whether or not some set of
             | symptoms was lupus. Then I closed my laptop, tired of
             | wasting my time. I sat quietly on the couch in my living
             | room for a moment. My wife was watching television in the
             | next room over, at a volume where the dialogue was clearly
             | audible, and what do I hear but a woman state, "At that
             | time, I was diagnosed with lupus"!
        
               | dylan604 wrote:
               | Next, you'll see it appear in your social targeted ads.
               | <cueOmninousMusic>
        
       | jonplackett wrote:
       | 90% of House MD plots ruined
        
         | ramon156 wrote:
         | I don't even need to read the article, the answer is more mouse
         | bites
        
         | m463 wrote:
         | but it was never lupus anyway. mostly.
        
           | Tagbert wrote:
           | It was Agatha, all along.
        
         | orbat wrote:
         | Maybe if one more painfully unfunny person repeats this tired
         | joke that we see every time lupus is mentioned, it'll finally
         | be funny. Let's find out!
        
           | johnnyanmac wrote:
           | To each their own. was a funny and nostalgic throwback. I
           | haven't watched House in 15 years and haven't even seen it
           | referenced since pre-pandemic.
        
         | AdmiralAsshat wrote:
         | To be fair, House's plots usually reiterated, "It's never
         | Lupus."
         | 
         | (And the one time it actually was had a rather disappointing
         | reveal, IMO)
        
         | fragmede wrote:
         | Time to bring it back for an special episode where House say's
         | it's not lupus, but it turns out it is and they find out thanks
         | to an intern, and then they cure it using this new therapy.
        
       | casper14 wrote:
       | My girlfriend has lupus, so I showed her the article. It sparked
       | a bit of hope. She has a science background and always asks in
       | awe "how do you find such good papers on the day they get
       | released". She's not really the HN audience though :*)
        
       | JaggerFoo wrote:
       | Nick Cannon, host of "The Masked Singer" America, would be glad
       | to hear this. He has Lupus.
       | 
       | Now all he needs is a cure for poor "Pull-Out" game syndrome.
       | 
       | Cheers
        
       | hsuduebc2 wrote:
       | Let's hope that from eczema to lupus all these mysterious
       | autoimmune diseases would be at least explained if not
       | eradicated.
        
         | riley_dog wrote:
         | Agreed. I sure would love to eat gluten.
        
         | wkcheng wrote:
         | I wonder if allergies can eventually be fixed somehow as well.
         | There has to be an immune or autoimmune reason why some people
         | have tons of allergies and other people are perfectly fine.
        
           | theGnuMe wrote:
           | Allergies are caused by an overactive immune system. The way
           | to overcome them is to train the immune system by exposing
           | yourself to low doses of the allergen. Doctors do this and
           | it's called allergen immunotherapy. Interestingly this has
           | been done since 1911.
           | 
           | https://www.nature.com/articles/s41577-022-00786-1
        
             | anonzzzies wrote:
             | I used to be allergic to 100s (I could not even walk 1
             | meter of certain weeds and I would get blisters etc) of
             | things until I moved away from my country 20+ years ago. I
             | suddenly was allergic (as far as I know still now) to
             | nothing; I accidentally came in contact with some of the
             | worst allergens of old (as I live in nature since then) and
             | they did nothing to our surprised. My wife who was allergic
             | to seafood (passing out to needing epi levels) and that's
             | gone too, shortly after the move. I don't know why; our
             | doctor then didn't know, but we chalked it up to stress; we
             | went from depressing commute ratrace city jobs to sitting
             | in a forest in nature doing whatever we liked. I work more
             | hours now but they are stressless. Don't know whatever is
             | true, but one mistake I made was not moving earlier.
        
               | lynguist wrote:
               | From where to where did you move then?
        
               | anonzzzies wrote:
               | NL -> ES
        
               | emacsen wrote:
               | It sounds like you moved to Stardew Valley.
        
               | anonzzzies wrote:
               | Certainly looks and feels like it
        
           | hanniabu wrote:
           | Largely depends on gut microbiome
        
         | hliyan wrote:
         | I've had some sort of autoimmune thing hitting me almost every
         | decade of my life (and then clearing up): eczema, asthma,
         | vitiligo and most recently psoriasis. Usually quite mild, but I
         | worry that the next one in the progression will be arthritis.
         | Most doctors' explanations can be summarised into a shrug.
         | Would be a relief to know what's going on in there.
        
           | psychopomp wrote:
           | Autoimmune disorders all have a common root of gut
           | dysfunction. I suffered from chronic inflammation for five
           | years, the ultimate solution was a double capsule probiotic
           | and eating more fiber. Most probiotics have a single capsule
           | that opens in the stomach and all those CFUs are killed by
           | stomach acid.
        
             | hanniabu wrote:
             | Sad to see you're getting down voted, shows how far behind
             | everyone is
        
             | xlbuttplug2 wrote:
             | Any particular strain/brand that helped for you?
        
               | psychopomp wrote:
               | I use and recommend Seed https://seed.com
        
           | spondylosaurus wrote:
           | Hey: do you have any stomach problems? Because that was me
           | (up to and including the arthritis part) and then my "IBS"
           | turned out to be Crohn's disease and once I started treating
           | that 90% of my other shit vanished. Things were so bad back
           | then that I was seriously considering a hip replacement to
           | make the pain stop, but today I just hopped off the exercise
           | bike and feel totally fine.
        
             | xlbuttplug2 wrote:
             | What was the treatment in your case?
        
               | spondylosaurus wrote:
               | At first, a mix of mesalamine and oral steroids; then I
               | graduated to Remicade and a low dose of methotrexate to
               | stop my immune system from creating antibodies against
               | the Remicade. And that's basically it.
               | 
               | I should also note that even when I was _only_ taking
               | mesalamine (a drug that works in your GI tract and
               | basically nowhere else), my arthritis pain improved
               | drastically, so it wasn 't just the result of steroids
               | having a general anti-inflammatory effect. Treating my
               | intestines alone was enough for me to stop walking with a
               | cane.
        
             | hliyan wrote:
             | Oh dear, I hope not. I do tend to have the occasional need
             | to visit the mens room several times a day (but only at a
             | level where it's just the mildest of inconveniences). I'd
             | be really worried if it was IBS. The prospect of that
             | getting "upgraded" to Crohn's is downright terrifying.
             | Maybe I'll ask my GP next time.
        
               | spondylosaurus wrote:
               | It could very well not be that, but I always feel
               | compelled to mention it just in case I can spare someone
               | else the same "three years of confusion to figure out
               | what was wrong" fate that I suffeed :P
               | 
               | And even more broadly speaking, if your immune stuff does
               | progress, the good news is that treating the biggest
               | baddest one (in my case, the Crohn's) usually treats the
               | myriad smaller ones with it. So if you ever end up
               | arthritic enough to get treated for that, the treatment
               | should knock down your psoriasis and other stuff too!
        
               | junto wrote:
               | Several times a day especially if it feels urgent, is
               | unusual. If you see any blood in your stool then visit a
               | doctor as soon as you can.
        
               | spondylosaurus wrote:
               | ^ Likewise if certain foods set you off _and_ those foods
               | are actually  "good for you". If you feel like crap after
               | eating a ball of grease, that's one thing, but it turns
               | out leafy greens aren't supposed to give you a nuclear-
               | level stomachache.
        
           | neom wrote:
           | What type of vitiligo?
        
         | alexey-salmin wrote:
         | There is a study that claims that genes associated with
         | autoimmune diseases increased survival during the black death
         | epidemic by 40% and frequency of these genes increased a lot in
         | the 14th century Europe [1]. I haven't yet seen independent
         | confirmations but I can imagine that paranoid immune system can
         | be beneficial depending on circumstances. If we eradicate
         | autoimmune diseases then there's a chance we won't survive the
         | next big pandemic.
         | 
         | [1] https://www.nih.gov/news-events/nih-research-matters/how-
         | bla...
        
           | wyldfire wrote:
           | > If we eradicate autoimmune diseases then there's a chance
           | we won't survive the next big pandemic.
           | 
           | IMO it seems more likely that we'd find effective treatment
           | which mitigates symptoms of autoimmune disease than a
           | treatment that irreversibly eradicates the disease (including
           | from subsequent generations, even?).
        
       | erichanson wrote:
       | My sister just got diagnosed with lupus.
        
       | bionhoward wrote:
       | Anybody have a PDF? Would love to learn more!
        
       | zeagle wrote:
       | This group presented an abstract at ACR in the fall prior so it's
       | nice to see it published now.
       | https://acrabstracts.org/abstract/cxcl13-t-cell-differentiat...
       | if you don't have journal access to the Nature article.
       | 
       | Kudos to them for landing a nature publication but I really would
       | temper this level of excitement (??a top link on HN??) at a basic
       | science research publication discussed in a press release from a
       | university highlighting it's researchers.
       | 
       | My read is it is down to decreased CXCL13 expression and type I
       | interferon expression in blood of a small number of patients,
       | controls, and cell culture which gives direction for further
       | study. CXCL13 was published as a possible RA biomarker half a
       | decade ago and crickets since then clinically. Is it causal or a
       | consequence of chronic inflammation? Type I interferon signature
       | has been looked at heavily for over a decade and is clearly
       | relevant in SLE but still only just over about half of lupus
       | patients have it and the signature is by definition broad
       | expression of hundreds of genes that affect innate and adaptive
       | immune system components.
       | 
       | We DO need better treatments for lupus patients but it's a very
       | variable disease in severity, clinically, and in terms of
       | biomarkers making it difficult. I mean the best drug that
       | everyone with lupus should be on barring a good reason is an old
       | antimalarial (that doesn't treat COVID) and then we add to it. If
       | you are interested in other new-ish therapies for lupus take a
       | look at anifrolumab, belimumab, voclosporin, and even newer CAR T
       | stuff. Important to consider the manifestations being treated
       | with those in the studies e.g. belimumab with skin, joint, kidney
       | but nothing for hematologic/cardiac/neurologic manifestations.
        
         | Kalanos wrote:
         | I don't have much context, but the identification of the AHR
         | receptor for the CXCL seems like the exciting part.
         | 
         | From what I understand, it is easy enough to design an antibody
         | once you know the right receptor to target
        
         | fasa99 wrote:
         | Exactly. When our car doesn't run well, a car with perhaps
         | 20,000 parts, we take it to the mechanic who says "yup, issue
         | was your spark plug, fixed". And even then, of course, the car
         | issue may have been multifactorial. Maybe the spark plug failed
         | because the fuel/air mix was off, for example, the spark plug
         | was the symptom.
         | 
         | But then we leap from the car with 20,000 parts to a body with
         | a trillion cells each cell with a trillion molecules. The
         | calculus of the fuel/air mix and the spark plug has now been
         | blown out of proportion, as challenging as conceiving a 20
         | dimensional manifold or the size of the universe. And so my
         | reservation with a paper like this, and in general, is people
         | say, "yup, sure was the spark plug" and then get accolades and
         | a Nature paper, when the core issue was the air fuel mix, the
         | air fuel mix that is, times a trillion cells, times a trillion
         | molecules.
         | 
         | And I can't blame the authors. No shame in shooting for Nature
         | and succeeding. No shame in these simplistic models, each one
         | takes us a step further. But somewhere along the lines we're
         | going to have think about the R&D of the big picture in non-
         | hand-wavey ways.
        
           | _Adam wrote:
           | > But somewhere along the lines we're going to have think
           | about the R&D of the big picture in non-hand-wavey ways.
           | 
           | How?
        
             | aftbit wrote:
             | Superintelligence
        
               | pixl97 wrote:
               | Probably not a great solution....
               | 
               | When dealing with code we say refactor and simplify.
               | Superintelligence my (rightfully) consider us too
               | complicated and a 'big ball of mud' and replace us with
               | version 2.0.
        
             | nanomonkey wrote:
             | Likely nanotechnology. Sensors that can reside in your body
             | and give up to the moment details, and chemical factories
             | that we can programmatically make adjustments to the body's
             | existing pathways (reprogramming the immune system, etc.).
             | 
             | In other words, better integration and faster feedback
             | loops.
        
               | pixl97 wrote:
               | Just wait till some small percentage people have random
               | immune responses to the nanotechnology just creating
               | another feedback loop in the system.
        
           | the_sleaze_ wrote:
           | The thing about a car is when the bumper gets detached you
           | can't just strap it down to the front of the car and wait
           | until it reattaches itself.
           | 
           | It may be (surely is) that something like lupus is
           | multifactorial and impossibly complex, but knocking out the
           | largest cause of something can be a reliably cure.
           | 
           | Look at antibitoics - a truly "replace the sparkplug" fix for
           | let's say treating a MRSA infection. Doesn't treat cell
           | damage, doesn't treat inflammation, doesn't treat pain,
           | doesn't treat hormonal imbalance through the body. It doesn't
           | even target the specific infection it kills indiscriminately.
           | Yet "give them antibiotics until the MRSA goes away, or if it
           | doesn't give them more antibiotics until it does" it super
           | hand-wavy.
        
           | Finnucane wrote:
           | Sure, a car has a lot of parts, but when one of them is
           | leaking oil where it's not supposed to, you don't have to
           | check every part to see where the problem is.
        
         | w10-1 wrote:
         | Yes, pathways are complex and adaptive, but as I read the
         | abstract (thank you!), they're suggesting a treatment path.
         | 
         | The potential treatment is that the protein JUN can block IFN's
         | increasing CXCL13 pathologically.
         | 
         | It's testable in that JUN itself can be produced and delivered
         | during acute phases to reduce flares, and could itself be a
         | therapy.
         | 
         | More lasting gene diagnostics and therapies may come from
         | checking for dysregulated genes in the pathway and injecting
         | genes to produce JUN.
         | 
         | It's not promising, though, to the extent JUN wouldn't address
         | an underlying IFN dysregulation.
        
       | notheyarent wrote:
       | they aren't cell diseases. It is plant toxins either leaking into
       | the blood stream through intestinal permeability or a problem
       | with peoples livers being fatty and not able to do their job
       | anymore resulting in the bodies inability to remove plant toxins.
       | The toxins cause an immune reaction wherever they build up ,
       | rheumatoid arthritis if it's the joints of the legs and arms etc.
       | 
       | Plant toxins include pesticides, fungicides, herbicides, both
       | human created and sprayed on and natural ones to stop animals and
       | bugs eating them. They also include glysophate
       | 
       | Thousands of people on Reddit have put Rheumatoid arthritis and
       | other Auto immune diseases into remission using the carnivore
       | diet. Ie manually removing Plant toxins from their food and not
       | letting the toxins enter their damaged bodies
        
         | geewee wrote:
         | If these toxins build up in animal cells - why would you eating
         | meat (that must then have a much higher concentration) not
         | expose you to the same toxins?
        
           | seaal wrote:
           | The trick is you must eat meat that only ate meat!
        
             | geewee wrote:
             | It's meat all the way down!
        
         | colordrops wrote:
         | This idea that plants are toxic and meat is healthy is absurd
         | in the extreme. Historical evidence shows humans at mostly a
         | plant based diet for most of our evolution. And the various
         | large and strong herbivores are completely contradictory to
         | your thesis. It's similar to flat-earth in how easy it is to
         | debunk.
        
           | idunnoman1222 wrote:
           | the reason that this bro science works for people is that
           | change can effectuate change EG what you're doing isn't
           | working change what you are doing and that can have affect
           | with anything, mind, immune system, you name it, I had RA and
           | it went into remission when I just changed my diet and
           | started eating totally different foods. Now we can say that
           | those foods were the cure all and that everyone eat them, but
           | maybe just change your life a bit You're doing right now
           | ain't working
        
         | theferalrobot wrote:
         | Wouldn't then the cure just be to eat organic food, rather than
         | meat of animals that were fed way worse crap than the average
         | person? The whole premise makes no sense...
        
           | tuennesje wrote:
           | I believe no one diet works equally for every single
           | individual with Autoimmune conditions. For some, a plant-
           | based diet reduces symptoms, for others like Jordan B.
           | Peterson, and his daughter (I believe she suffered from RA) a
           | purely meat-based diet reduced all of their symptoms.
           | Personally, I struggle with Hashimotos, Ankylosing
           | Spondylitis and Crohn's Disease and have to stay away from
           | sugary foods, alcohol and caffeine or else one of the
           | conditions will flare up. Any type of meat is fine for me
           | however.
        
         | aroopchandra wrote:
         | For me, it was the opposite. Cutting out meat and eating a lot
         | of organic greens helped calm my immune system and reduce
         | inflammation. In my experience, meat increased my inflammation,
         | while greens decreased it. I think everyone is different, and
         | it's not hard to test on yourself if you have noticeable
         | symptoms like joint pain, as I did.
        
         | atombender wrote:
         | Funnily enough you have another poster [1] saying the exact
         | opposite, that meat makes their symptoms worse, and eating
         | plant foods makes their symptoms go away.
         | 
         | Whenever the carnivore diet comes up as a panacea (which it
         | does, a lot), I wonder if people tried anything else. Did they
         | try reintroducing plant foods to test their hypothesis?
         | 
         | Personally, I bet that it's not the diet itself that helps in
         | most cases, but that the very act of changing one's diet
         | radically alters the gut microbiome. People with autoimmune
         | diseases usually have a dysbiotic gut flora, so it makes sense
         | that a radical change would "reset" it. However, this would
         | suggest that reintroducing foods should work, unless you
         | reintroduce things that bring back the imbalance.
         | 
         | Anecdotally, my psoriasis disappeared after I switched to a
         | strict vegetarian diet. I can't prove it, though, so I don't go
         | on Reddit making unscientific claims I can't back up with
         | evidence.
         | 
         | [1] https://news.ycombinator.com/item?id=40937383
        
       | dpeckett wrote:
       | Fascinating stuff, it's interesting to read that the main ligands
       | of the AhR (Aryl hydrocarbon receptor) are PAHs (Polycyclic
       | aromatic hydrocarbons) and that activation of the AhR receptor
       | improves the markers of Lupus.
       | 
       | Polycyclic aromatic hydrocarbons are nasty, carcinogenic,
       | molecules that are commonly found in smoke, tar, and char.
       | Basically burnt organic matter. On the other side of the coin AhR
       | is also activated by a bunch of Polyphenols, which are found in a
       | variety of plant derived foods.
       | 
       | Does this mean, it is possible that Lupus (and Psoriasis) are
       | diseases of affluence caused by processed food (low in
       | Polyphenols), and a reduced exposure to smoke byproducts in the
       | environment?
        
         | NetOpWibby wrote:
         | That's wild, if true.
        
         | ta988 wrote:
         | Smoking is supposed to be a risk factor so who knows.
        
           | dpeckett wrote:
           | Man biology is weird, yeh it looks like for Lupus and
           | Psoriasis it pretty much doubles the risk of developing it.
        
         | caddemon wrote:
         | There's definitely a genetic component but it would be
         | interesting if those environmental factors impacted prevalence
         | or severity.
         | 
         | Autoimmune disorders in general might be worse/more common in
         | countries where kids grow up in clean environments. There's
         | already some discussion on this with regard to allergies that I
         | think has some credibility.
        
       | biosboiii wrote:
       | Whatever, it's never Lupus.
        
         | marton78 wrote:
         | Sometimes it is, a dear friend of mine is suffering from it.
         | It's a really bad illness.
        
         | instakill wrote:
         | Came here for the House comment. Amazing how that show owned
         | this word
        
           | andruby wrote:
           | I have a t-shirt with that comment. A few years later, a
           | family member gets diagnosed with Lupus. I stopped wearing
           | the t-shirt.
        
       | greenish_shores wrote:
       | Somebody pls upload this
       | https://www.nature.com/articles/s41586-024-07627-2 on sci-hub.
        
         | ck2 wrote:
         | try LibSTC
        
           | ta988 wrote:
           | It says "Sorry, the file is absent :("
        
             | ck2 wrote:
             | I am sure it will be there eventually.
             | 
             | This is a preprint of the abstract to the paper and I know
             | there are some very smart people on HN but if you can grasp
             | this you are in an entirely much higher orbit
             | 
             | https://acrabstracts.org/abstract/cxcl13-t-cell-
             | differentiat...
             | 
             | What's interesting is that AHR is also involved in Covid
             | infections so this will highly likely be further
             | researched.
        
       | humanlity wrote:
       | My father got this, I truly hope that can cure he
        
       | rpaddock wrote:
       | The Nightshade family of plants, which are very common in our
       | diets, can mimic the symptoms of Lupus. That food sensitivity
       | needs ruled out when diagnosing the cause of Lupus.
        
         | ta988 wrote:
         | Do you have research that shows that? What I've read is that
         | there was no real evidence of that.
        
           | weberer wrote:
           | He's likely referring to solanine poisoning.
           | 
           | https://en.wikipedia.org/wiki/Solanine
        
             | rpaddock wrote:
             | Yes. Also "inflammation and pain in the joints" can be
             | mistaken for Rheumatoid Arthritis (RA).
             | 
             | We discovered the hard-way that my late wife had issues
             | with this. Multiple doctors diagnosed her with both RA and
             | Lupus. When we got the Nightshades out of her diet and
             | switched to more natural based cleaning products, such as
             | Hemp based soap, shampoo and vinegar for cleaning, her
             | symptoms of RA and Lupus went away. An good allergist finds
             | things like this.
        
       | primer42 wrote:
       | Someone page Dr House!
        
         | mayormcmatt wrote:
         | It's not lupus!
        
       | aroopchandra wrote:
       | I was diagnosed with lupus a few years ago. My mom also had it
       | and passed away after 10 years due to complications. My initial
       | symptoms were severe joint pains, which made daily activities
       | difficult. This happened during the COVID lockdown, which helped
       | me maintain my job.
       | 
       | I did a lot of research and tried various treatments. Functional
       | medicines and expensive vitamins didn't help. I read about long-
       | term fasting and tried different routines at home. I did several
       | 1-day, 3-day, and 7-day fasts. During the 7-day fasts, my pain
       | disappeared, but it returned once I resumed eating. This led me
       | to believe that food was causing inflammation.
       | 
       | Previously, I ate a lot of lean meat and occasional red meat. I
       | then cut down to eating meat once a week and ate mostly raw leafy
       | vegetables the rest of the time. My pain would come back after
       | eating meat and decrease over the week. I eventually stopped
       | eating meat entirely and consumed a ton on greens, and within six
       | weeks, I was pain-free.
       | 
       | I also tried Benlysta for months, but it didn't help much.
       | Vegetables seemed to reduce my inflammation more effectively. I
       | stopped taking Benlysta but continued regular blood tests. After
       | a year, my doctor agreed I could stop the medication. I've been
       | in remission for the last two years with no pain or inflammation.
       | 
       | I hope this helps, though it's just my personal experience.
        
         | wholinator2 wrote:
         | I have crohn's disease which is also autoimmune and directly
         | related to ingesting certain things. I think a lot of
         | autoimmunity has to do with intestinal bacteria and their
         | relationship to our innate immune system. And to a lesser
         | extent it seems that almost every aspect of life is effected by
         | what we eat, how we feel, how we act, how we grow and die.
         | Maybe in 100 years we'll have fecal tests and bacteria pills to
         | catch and prevent a paradigm shifting amount of ailments.
         | 
         | I know I've tried tons of different diets and exclusions and
         | things. I've got a pretty good list in my head of what i can
         | and can't eat but it seems to change q bit every couple years.
         | I used to not tolerate bread but eat sugar and it seems to have
         | switched some time in the last decade. Anyways, i wish you luck
         | with your journey and I'm glad you've found something that
         | works for you
        
           | aroopchandra wrote:
           | I got fecal tests and used expensive supplements and vitamins
           | as recommended by a functional doctor, but they didn't help.
           | I looked into how immune suppression medicines like Benlysta
           | work and tried to mimic their effects naturally to get relief
           | and hopefully stop using medicine. I think food can help
           | manage many side effects of immune-related diseases, even if
           | it can't cure them.
        
             | lhoff wrote:
             | You might want to try the Wim Hof Method. I don't believe
             | in everthing Wim Hof attributes to his method but when it
             | comes to immune response, there is scientific evidence that
             | it does indeed result in an increase of IL-10, which is
             | anti inflammatory.
             | 
             | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034215/
        
           | nanomonkey wrote:
           | Quite a few of my friend's that were diagnosed with chron's
           | disease found out that the main culprit seemed to be flour
           | and other foodstuff that had been treated with glyphosate
           | (Roundup). After switching to sourdough bread made from
           | organic flours, and similar choices for masa harina
           | (nixtamilated corn) their issues went away. This was after
           | years of not eating anything with fiber, gluten, or
           | nightshades.
           | 
           | Their theory was that the herbicides would kill off their
           | gut's natural biome and cause an inability process
           | carbohydrates, fiber and maintain a intestinal mucus layer.
           | 
           | YMMV...but just passing along what has worked for a few of my
           | friends.
        
             | skrebbel wrote:
             | > after years of not eating anything with fiber,
             | 
             | You mean they avoided vegetables entirely?
        
               | blix wrote:
               | My doctor told me after an intestinal surgery that I
               | would never be able to eat vegetables again.
        
             | novok wrote:
             | There is also other things like brominated flour which is
             | illegal in brazil, the eu, india and canada but not the USA
        
               | geoelectric wrote:
               | California banned potassium brominate as a food additive
               | last year, but it doesn't go into effect until 2027.
               | 
               | The FDA _finally_ banned brominated vegetable oil very
               | recently so maybe they'll get to the rest of it too.
               | Assuming they can make rules anymore, anyway.
        
             | datavirtue wrote:
             | Hmmm...I recently had my gut biome die off but could not
             | identify any suspects. I bake a lot.
             | 
             | The most noteable thing about the whole experience was how
             | amazing my bowel functions are after having to restore the
             | gut biome. They are functioning far better than the many
             | years before I experienced the die off. I used pills from
             | Amazon that had good reviews (Physicians Choice) with a
             | strict raw vegetable diet, and they definitely worked. I
             | noticed another uptick in bowel function after taking some
             | pills my wife purchased that had more strains. You can't
             | just eat yogurt and dust off your hands.
        
             | smm11 wrote:
             | Happened with my "gluten-free" wife, too. No issue with
             | legit sourdough.
        
         | COGlory wrote:
         | I'm curious if you've looked into N-Glycolylneuraminic acid and
         | whether that could be the issue? Does chicken cause an issue
         | for you?
         | 
         | I'm sorry to hear about your Lupus diagnosis, and glad it's in
         | remission. My doctor wanted to diagnose me with Lupus due to
         | the facial rash and arthritis/joint pain, but I came back
         | negative in all the bloodwork, which I think means about 98%
         | sure don't have it. I found that I can treat the joint pain
         | effectively with SSRIs (Fluoxetine, 20 mg is enough to wipe it
         | out after a few weeks). My mother has MCAS and my sister and
         | aunt have UC, so I feel like I'm tripping through a minefield
         | trying to navigate whatever autoimmune issue this is....and I
         | have a PhD in biochemistry.
        
           | aroopchandra wrote:
           | I haven't looked into N-Glycolylneuraminic acid specifically.
           | For me, all types of meats, including eggs, chicken, and
           | lamb, increased my inflammation levels. From what I
           | understand, correctly diagnosing immune diseases can be quite
           | challenging. My doctor once said it's more of an art than a
           | science. Because my mother had lupus it was easy in my case.
           | While I'm not against medications, they often come with side
           | effects. For example, immunosuppressants are necessary for
           | high inflammation but can increase the risk of cancer. Even
           | SSRIs have side effects.
           | 
           | When I had pain, I tried both medications and dietary
           | changes, using an engineering mindset to isolate variables.
           | Although I listened to my doctor, I also took matters into my
           | own hands and did my research. My doctor initially doubted
           | that changing my diet would help but did recommend the
           | Mediterranean diet. He still doesn't believe that food helped
           | since there's no clinical research backing it, and it's not
           | something commonly taught in medical schools.
           | 
           | The best part about experimenting with food is that it's easy
           | and inexpensive to test on oneself. In my case, I was
           | fortunate that my joint pains allowed me to observe the
           | effects of my dietary changes within a week or less.
           | Initially, I expected results in a day or two, but I soon
           | realized that I needed to experiment for at least a few weeks
           | to see the full effects. These days, I consume small
           | quantities of eggs every few weeks and haven't noticed any
           | significant increase in inflammation.
        
           | tremon wrote:
           | _I came back negative in all the bloodwork_
           | 
           | One of my friends has APLS (antiphospholipid antibody
           | syndrome), which can also occur as a secondary symptom of
           | Lupus. All of her blood tests always come back negative due
           | to the way APLS affects coagulation -- unless the bloodwork
           | is cultured for at least two days. So if you have reason to
           | suspect the test results may be incorrect, ask them to re-do
           | the bloodwork as a long-term culture rather than the normal
           | fast screening.
        
         | maayank wrote:
         | What do you eat for protein in the current diet?
         | 
         | What was your experience with fish?
        
           | aroopchandra wrote:
           | I eat a lot of legumes such as lentils, chickpeas, black
           | beans, and peas. I also include tofu made from soy, and nuts
           | like almonds, peanuts, as well as seeds like chia, flaxseeds,
           | and hemp. I use plant-based protein powders too specifically
           | (https://lovecomplement.com/products/complement-organic-
           | vegan...) when I drink green smoothies (3 to 4 meals a week).
           | 
           | Green leafy vegetables also has a lot protein (Kale, Broccoli
           | and Brussels).
           | 
           | I use supplements for B12 which is missing from vegetable
           | foods.
           | 
           | I used to eat fish but when I stopped all animal products I
           | gave up fish as well. I guess if I have fish once in a while
           | it won't hurt me but I have a tendency to overdo it. The main
           | thing for me was to reduce the inflammation when I had the
           | imbalance. This meant stopping everything I thought might
           | cause inflammation until it went away.
           | 
           | My diet was also free of all salts, sugars and oils for few
           | months though I do use them now.
        
             | bumby wrote:
             | > _I use supplements for B12 which is missing from
             | vegetable foods._
             | 
             | Just in case you're looking for an inexpensive vegan whole
             | food source, seaweed sheets (like those used in sushi) have
             | a relatively high amount of B12. I took a look at the brand
             | in my pantry and it has 60% RDA per sheet.
        
               | aroopchandra wrote:
               | Thats a good idea. I will for sure add it to my snacks as
               | I actually like seaweed
        
             | schlick wrote:
             | Maybe a crazy take here but it sounds like the Lupus
             | actually made you healthier?
             | 
             | Either way congrats on finding a way towards living a happy
             | and healthy life, props to you.
        
               | aroopchandra wrote:
               | For sure it did make me healthier and know my body better
        
         | xdrone wrote:
         | In the vegan community there is lost of discussion of animal
         | products causing auto immune issues. A compromised gut lining
         | will let intact animal proteins into the body. The immune sees
         | the animal foreigners but also attacks our body; us being
         | animals too.
         | 
         | Type 1 diabetes, aka childhood diabetes, is thought to be from
         | casein in A1 milk; where the immune system attacks the beta
         | cells of the pancreas. Seems plausible to me; rates of dairy
         | consumption seem to correlate with type 1. (see Finland).
        
           | aroopchandra wrote:
           | I also read this in multiple places and trusted it. At least
           | that's how I internalized my condition when I started the
           | experiment.
        
           | valgor wrote:
           | Funny enough, I mentioned not eating meat on another
           | hackernews thread today and someone told me I'm going to get
           | an autoimmune disease.
        
         | loceng wrote:
         | Did you ever do an Igg food sensitivity test-food panel to
         | check if there were any inflammatory Igg markers from specific
         | foods you were eating? E.g. they can test for 200+ most common
         | foods, which you would of had to have eaten within the last 2-3
         | months for the Igg markers to still be present - otherwise they
         | breakdown and obviously won't be detected.
         | 
         | To note, you need to eat high fat meat in order to properly
         | digest the meat.
         | 
         | It's possible to also be allergic to certain types of meat,
         | e.g. there's a protein in duck that bothers me.
         | 
         | Another factor to seriously consider is if consuming high
         | quality organic meat vs. whatever else.
         | 
         | Also, meat requires a lot of energy to break down due to its
         | [nutrient-calorie] density - of course you get back much more
         | energy than it consumes, but it is an intensive process, so if
         | there are other foods you're eating that are causing irritation
         | then digesting meat could be problematic - and so then while of
         | course reducing or stopping eating meat will then stop
         | symptoms, it's possible that if removing the other foods that
         | may be causing problems would then allow the meat consumption
         | without causing any problems.
         | 
         | There's really been no properly done research on diet.
        
       | spdustin wrote:
       | HLA-B27 is directly related to a number of autoimmune disorders,
       | including lupus. I hope this research can expand to other
       | conditions associated with HLA-B27, like psoriasis, psoriatic
       | arthritis, ankylosing spondylitis, etc.
        
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