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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

#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 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.

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

#72
post #55

Let's hope that from eczema to lupus all these mysterious autoimmune diseases would be at least explained if not eradicated.

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.

What type of vitiligo?

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

#73
post #40

Earlier quoted context omitted.

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.

> 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.fr…

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.

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

#74

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…

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.

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

#75
post #54

Earlier quoted context omitted.

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…

Is this why something like vitamin C can help with depression?

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.

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

#76

Earlier quoted context omitted.

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.

Any particular strain/brand that helped for you?

I use and recommend Seed https://seed.com

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

#77
post #50

Earlier quoted context omitted.

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.

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

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.

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

#78

Earlier quoted context omitted.

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…

And some autoimmune treatments started out as failed attempts at developing cancer treatments, too. Happy accidents!

I <3 all the happy accidents that allow us to live much healthier and longer lives than the generations before us

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

#79

Earlier quoted context omitted.

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

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…

From where to where did you move then?

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

#80

Earlier quoted context omitted.

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…

From where to where did you move then?

NL -> ES
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