Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Scientists discover a cause of lupus, possible way to reverse it

news.feinberg.northwestern.edu

Post reply on HN
Print view View original

91–100 of 201 posts

Re: Scientists discover a cause of lupus, possible way to reverse it

#91

Post by dg08 »

atombender wrote: post #8
BenFranklin100 wrote: post #4

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…

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. I…

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.

Re: Scientists discover a cause of lupus, possible way to reverse it

#92

Post by theferalrobot »

notheyarent wrote: post #86

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, fungi…

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...

Re: Scientists discover a cause of lupus, possible way to reverse it

#93

Post by hliyan »

spondylosaurus wrote: post #58
hliyan wrote: post #55

Earlier quoted context omitted.

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.

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.

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.

Re: Scientists discover a cause of lupus, possible way to reverse it

#94

Post by dpeckett »

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?

Re: Scientists discover a cause of lupus, possible way to reverse it

#96

Post by meindnoch »

hanniabu wrote: post #70
steelframe wrote: post #26

Earlier quoted context omitted.

> 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 t…

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.

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.

Re: Scientists discover a cause of lupus, possible way to reverse it

#97

Post by carynh »

avgDev wrote: post #14
ipunchghosts wrote: post #2

I wonder if any of these findings help us better understand me/cfs.

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 w…

> 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!

Re: Scientists discover a cause of lupus, possible way to reverse it

#100

Post by atombender »

A_D_E_P_T wrote: post #36
atombender wrote: post #8

Earlier quoted context omitted.

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. I…

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'-diindolylm…

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...

Post reply on HN