Stanford: Scientist identify the underlying cause of rheumatoid arthritis

Belbyr

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http://med.stanford.edu/news/all-ne...N8vVv12VaG7ZzgU-JbX6aXhQ76Q7Nl2aNngURzGngCfqM

The errant cells are helper T cells. After infiltrating synovial tissue, they send out signals that call in other super-aggressive immune cells and cause ordinary synovial cells to become inflamed and destructive.
In prior work, Weyand’s group noticed telling differences between the helper T cells of patients with rheumatoid arthritis and those of healthy people. The former, for instance, have low reserves of a molecule called ATP, which serves as cells' internal energy currency, accepted by all of a cell’s myriad metabolic enterprises. Yet instead of directing their primary energy source, glucose, toward ATP production, these cells divert their glucose supplies toward fashioning various materials — proteins, nucleic acids, membranes and the like — used to build new T cells that will contribute to further damage.
That shouldn’t happen. Like all cells, T cells contain AMPK, a regulatory molecule that senses ratios of ATP and its two main breakdown products. If it finds ATP too outnumbered by these breakdown products, AMPK clamps down on the T cell’s cell-building program and, instead, sends glucose off to the cell’s ATP-generating apparatus.
“When your house is cold, you need to throw your logs into your fireplace, not use them to build a new house in your backyard,” Weyand said.
The new study provides an answer to the question of why AMPK fails to perform its energy-monitoring function in the faulty helper T cells of patients with rheumatoid arthritis.
 

Judee

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I'm wondering, is this the first major finding of an underlying cause of an autoimmune disease?
I'm not sure but that's what I was thinking too. My grand-niece has Lupus so it would be wonderful if there could be a breakthrough with that (and the other autoimmune diseases) too. :D

Edit: Not to mention ME/CFS if possible.
 

Mary

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Thanks @Belbyr for posting this! :thumbsup: one of my sisters has RA, I'm going to forward the studies to her. She's fortunate in that she's not severely ill - she's able to function with a low dose of prednisone and Advil, but of course long-term they're not good, but she needs them to be able to function without too much pain.
 

Belbyr

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@Belbyr How does this new info relate to using Rituximab for RA (since it is FDA approved for RA) or does it not relate?
That is an interesting question. From my limited knowledge of immune cells, I read that T cells have nothing to do with autoimmunity, which this article says the opposite... So either I am confused or the flood gates opened up with this new finding?
 

Belbyr

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Thanks @Belbyr for posting this! :thumbsup: one of my sisters has RA, I'm going to forward the studies to her. She's fortunate in that she's not severely ill - she's able to function with a low dose of prednisone and Advil, but of course long-term they're not good, but she needs them to be able to function without too much pain.
I know 2 people with RA, one is a severe case and she is older the other is a girl younger than me that has 2 other autoimmune disease. I believe lupus and MS or something like that...
 

prioris

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doctor in australia found cure for most arthritis decades ago ... 12 mule team borax ... cost $5
Israel has lowest rate of RA in world ... their water supply has highest boron content in world
 

Belbyr

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doctor in australia found cure for most arthritis decades ago ... 12 mule team borax ... cost $5
Israel has lowest rate of RA in world ... their water supply has highest boron content in world
If that was the case, there would be no more RA. Even if what you said was true, the science behind it still needs to be found.
 

prioris

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If that was the case, there would be no more RA. Even if what you said was true, the science behind it still needs to be found.
borax cure rate was 70% …
most people with RA will never do the research ... they rely on doctors to tell them what to do
and told there is no cure hence they will never be cured
 
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Gingergrrl

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That is an interesting question. From my limited knowledge of immune cells, I read that T cells have nothing to do with autoimmunity, which this article says the opposite... So either I am confused or the flood gates opened up with this new finding?
I found that confusing/interesting as well since my understanding is that B-cells create (or control?) autoimmunity and not T-cells. Is this a totally new finding or just something that we did not understand?
 
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"We’ve learned that rheumatoid arthritis is, at root, a problem of faulty cell metabolism and, in particular, of one type of immune cell’s inappropriate diversion of resources from generating energy to the production of an army of inflammatory offspring,” she said. This cellular army exits the lymph nodes, makes its way to synovial tissues, takes up residence there and instigates the inflammatory damage that’s the hallmark of rheumatoid arthritis.

“We know how these immune cells fuel their bad behavior,” Weyand said. “And now we’ve shown we can reverse this behavior and make these cells behave as they should."

This is great work and there is relevance for us.

Onset patterns for RA are similar to ME/CFS (mostly women). RA has suspicious links to ebv. There is t-cell clonal expansion in RA just like in mecfs. we also may well have issues with AMPK.

Best-case scenario hypothetical: for people with a certain cluster of genes their t-cell ampk problems manifest in RA. For people with other genes their t-cell ampk problems manifest in me/cfs. The drug they are talking about testing solves the problem at the root and cures both!

(nb I think this best case scenario is highly unlikely. But I also think research from beyond the traditonal mecfs teams is as likely to help us as research from within. There's just more researchers outside our field than in it...)
 

nandixon

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I found that confusing/interesting as well since my understanding is that B-cells create (or control?) autoimmunity and not T-cells. Is this a totally new finding or just something that we did not understand?
There are a number of different types of autoimmunity. B-cell driven disease can cause autoantibody-related autoimmunity, which is probably what most people are familiar with, but that is just one type of autoimmunity.

“Autoimmunity” is just a general term for the immune system attacking healthy body components. Depending on the type of autoimmune disease it can be driven by either B cells or T cells - or both or neither.
 

prioris

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I found that confusing/interesting as well since my understanding is that B-cells create (or control?) autoimmunity and not T-cells. Is this a totally new finding or just something that we did not understand?
Like me decades back, doctor considered the father of autoimmune treatment thought it was very odd that the body would attack itself too ... the definition has external causes ... treatment does also e.g. AIP ... the term has been brainwashed into the minds of many people ... i always view autoimmunity as external causes ... not the body attacking itself
 
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Gingergrrl

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It seems like the number of illnesses that have suspicious links to EBV is growing by the day! (And I am saying this in complete seriousness and not being sarcastic).

But I also think research from beyond the traditonal mecfs teams is as likely to help us as research from within.
I believe that some day there will be some research break-throughs that are going to apply to many different diseases and that the me/cfs researchers are going to find stuff that helps people far and wide (and on the flip-side, non me/cfs researchers may just find the cure for me/cfs).

There are a number of different types of autoimmunity. B-cell driven disease can cause autoantibody-related autoimmunity, which is probably what most people are familiar with, but that is just one type of autoimmunity.
My doctor views my case as B-cell driven autoimmunity but I was not sure if this is b/c of the specific autoantibodies that I have or b/c of other factors? (and I do not have RA).

“Autoimmunity” is just a general term for the immune system attacking healthy body components. Depending on the type of autoimmune disease it can be driven by either B cells or T cells - or both or neither.
Thank you and I did not realize that (or did not retain it). Although I do now recall someone (maybe even you?) telling me in the past that the Hashimoto's autoantibodies are T-cell driven (and I do have both of those).
 

nandixon

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Best-case scenario hypothetical: for people with a certain cluster of genes their t-cell ampk problems manifest in RA. For people with other genes their t-cell ampk problems manifest in me/cfs. The drug they are talking about testing solves the problem at the root and cures both!

(nb I think this best case scenario is highly unlikely...
Unfortunately that seems right, because if the best case scenario were true then a large percentage of us would probably have found that taking rapamycin (aka sirolimus/Rapamune) would be an effective treatment.

In the full text of the scientific publication that the article in the original post is based on, the authors found that:

In vitro studies confirmed that activating AMPK with A769662 and inhibiting mTORC1 with rapamycin had equal potency to suppress pro-inflammatory T cells…

N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation
https://www.ncbi.nlm.nih.gov/pubmed/30718913/
 
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ScottTriGuy

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Unfortunately that seems right, because if the best case scenario were true then a large percentage of us would probably have found that taking rapamycin (aka sirolimus/Rapamune) would be an effective treatment.

In the full text of the scientific publication that the article in the original post is based on, the authors found that:
I fall into the Rapamune responder group, though (as I've said elsewhere on PR) after hearing a podcast interview with David Sabatini (the / a leading rapamycin researcher) saying that it should not be taken daily for long periods (will mess up mTor2), I decreased from 1mg daily to 1mg every 3rd day (as per his intimation), and my function and quality of life dropped off.

I wrote Sabatini for clarification if he was only speaking of healthy people, but did not receive a reply.

I'm thinking of returning to 1mg daily for a month or so.