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

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

#111
post #71

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 univers…

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

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

#112
post #97
post #14

Earlier quoted context omitted.

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!

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://en.m.wikipedia.org/wiki/Muscarinic_receptor_antagoni...

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

#114

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…

That’s wild, if true.

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

#115

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…

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.

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

#117

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…

Smoking is supposed to be a risk factor so who knows.

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

#118

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.

Do you have research that shows that? What I've read is that there was no real evidence of that.

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

#119

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…

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.

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