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.

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

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.

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.

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.

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.

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.

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.

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).

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.

Either way congrats on finding a way towards living a happy and healthy life, props to you.

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.

    > A 2014 study reported that dried purple laver ("nori") contains vitamin B12 in sufficient quantities to meet the RDA requirement (Vitamin B12 content: 77.6 μg /100 g dry weight).[19] By contrast, however, a 2017 review concluded that vitamin B12 may be destroyed during metabolism or is converted into inactive B12 analogs during drying and storage.[20] The Academy of Nutrition and Dietetics stated in 2016 that nori is not an adequate source of vitamin B12 for humans.[21]

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.

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.

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.

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.

In other words, better integration and faster feedback loops.

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.

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.

From what I understand, it is easy enough to design an antibody once you know the right receptor to target

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?

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.

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.

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...

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.

  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.

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...

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...

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.

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...

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 [email protected].

Many thanks!

[1] https://www.biorxiv.org/content/10.1101/2022.04.26.489314v5

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.

Just as antivirals are actually ‘stop cell division’

Neither of which inspire any confidence

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.

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.

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/

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.

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.

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.

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.

" 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.

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.

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!

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.

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.)

"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."

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.

The more important parts of their programs are the omics and tissue biopsy programs.

May they hopefully turn the ship…

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!

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.

[1] https://www.nih.gov/news-events/nih-research-matters/how-bla...

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?).

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