Stanford: Scientist identify the underlying cause of rheumatoid arthritis

nandixon

Senior Member
Messages
1,020
Likes
2,803
I'm thinking of returning to 1mg daily for a month or so.
I'll be interested if going back to daily improves things again for you. When I tried it, I felt better for a few days then worse, unfortunately (and I tried a number of different dosing strategies to try to recapture the good effect to no avail).

Interestingly, one of the most helpful sustainable treatments on this forum, anecdotally, appears to be supplementing with branched chain amino acids (BCAs). These, especially leucine, are probably the simplest way of stimulating mTOR, i.e., of achieving the seemingly opposite effect of Rapamune. But BCAs weren't helpful for me either, though.
 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,285
Likes
5,208
Location
Toronto, Canada
branched chain amino acids (BCAs). These, especially leucine, are probably the simplest way of stimulating mTOR, i.e., of achieving the seemingly opposite effect of Rapamune
For me, the Rapamune litmus test will be about a doubling in my exertion window. Currently I'm maxed out at 15 minutes walking on flat ground (not carrying anything) and I would expect to get back to a 30 - 45 minute walk, and if I do go over my exertion window, PEM will be much less intense and shorter duration.

Hhhmmm, I've been taking BCAAs (containing leucine) for at least a few years. Perhaps they are impeding Rapamune's effect and I should stop BCAAs while increasing Rapamune and see the effect?
 
Messages
31
Likes
115
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?
Thanks @Belbyr for posting this interesting piece.

Regarding the B and T cells in autoimmunity - there is a very interesting paper that was published in 2018 in frontiers of immunology called
"T Cell/B Cell Collaboration and Autoimmunity: An Intimate Relationship"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119692/

The authors "suggest that a significant beneficial impact of B cell depletion in autoimmune settings may be its detrimental effect on T cells engaged in molecular conversation with B cells." Maybe this helps with regard to @Gingergrrl 's question, why Rituximab is used and helps RA?

Hhhmmm, I've been taking BCAAs (containing leucine) for at least a few years. Perhaps they are impeding Rapamune's effect and I should stop BCAAs while increasing Rapamune and see the effect?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852795/#s6title

@ScottTriGuy

Maybe this paper helps: It has some dietary intervention strategies that inhibit mTOR - we are talking mostly about caloric restriction because in my opinion very low protein diets carry their own problems.

I hope it is okay to chime in :angel: I have several AI diseases and inhibiting mTOR and regulating autophagy is one of the few mechanisms that made me consider a fasting mimicing diet or periodic fasting, but with our disease one has to make sure to not lose any more strength than we have lost already...

Do you get monitored regarding your blood levels of rapamune because as I understand it, there is a high personal variability in metabolizing mTOR inhibitors ?

This is my first post - so I hope, I did not do anything wrong with the quoting and the papers and by just chiming in :angel:
 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,285
Likes
5,208
Location
Toronto, Canada
Do you get monitored regarding your blood levels of rapamune because as I understand it, there is a high personal variability in metabolizing mTOR inhibitors ?
Nope, no monitoring of blood levels of rapamune. Nor has it been suggested by my docs, but maybe I'm the one who needs to do the suggesting since I'm the one who requested it.

For the last 6+ months I have been fasting for 14 - 15 hours each day (well, mostly night) but haven't really noticed any effect, but I'm banking on long term benefits. My body seems to need lots of protein, and I minimize carbs, but yeah, keeping muscle and being inactive is a challenge.

Fwiw, in November I switched to Truvada for the Tenofovir for its potential impact on B cells. Curiously, I started to become hyperthyroid (according to tests) and have since lowered my dessicated thyroid (But I also have an empty sella and that could be messing my endocrine.) and my liver enzymes (ALT and AST) became elevated.
 

andyguitar

Senior Member
Messages
1,054
Likes
2,484
Location
South east England
As @Gingergrrl has noted some sufferers also have autoimmune disorders. It is often the case that they had them before getting ME/CFS so the possibility there is a link is -for at least some- there. Just one small bit of info from me on what is a big subject. The Amino Acid Histidine stimulates the activity of suppressor T-Cells. Looking at the theraputic uses of it, some of its functions fit some symptoms of ME/CFS. So might be worth a try for those who are not worried about its related chemical Histamine.
 
Messages
94
Likes
252
For me, the Rapamune litmus test will be about a doubling in my exertion window. Currently I'm maxed out at 15 minutes walking on flat ground (not carrying anything) and I would expect to get back to a 30 - 45 minute walk, and if I do go over my exertion window, PEM will be much less intense and shorter duration.

Hhhmmm, I've been taking BCAAs (containing leucine) for at least a few years. Perhaps they are impeding Rapamune's effect and I should stop BCAAs while increasing Rapamune and see the effect?
I'm a rapamune responder and I have to say that when I tried BCAAs (that was mostly leucine,) I just felt sick and quit it after the first try.

Good luck with your exertion goal. Let us know how you do.
 

Gingergrrl

Senior Member
Messages
14,255
Likes
42,578
The authors "suggest that a significant beneficial impact of B cell depletion in autoimmune settings may be its detrimental effect on T cells engaged in molecular conversation with B cells." Maybe this helps with regard to @Gingergrrl 's question, why Rituximab is used and helps RA?
That is interesting and I keep hearing more about Rituximab also affecting T-cells (in some capacity?) but I never quite understood this (and still don't o_O).

This is my first post - so I hope, I did not do anything wrong with the quoting and the papers and by just chiming in :angel:
It is great to see you posting @LiLaLu and please jump in anywhere!

As @Gingergrrl has noted some sufferers also have autoimmune disorders. It is often the case that they had them before getting ME/CFS
I often wonder if it is the opposite (re: ME/CFS and have no idea about RA). My case started out viral from severe Mono from EBV in 2012 and then approx 10 mos later it reactivated and I had a post-viral fatigue syndrome plus developed very severe POTS with HR going into the 160's and 170's on a daily basis. I matched on many (but not all) criteria of ME/CFS and this diagnosis was given to me by three different doctors.

Slowly, the viral symptoms completely disappeared and everything shifted into autoimmunity starting with Hashimoto's Disease and ending with the POTS being Autoimmune, severe MCAS, and several other autoantibodies including the LEMS (calcium channel) autoantibody. My symptoms in 2015 onward were very different than my symptoms in 2013. I became a much closer match to LEMS (which is autoimmune) than to ME/CFS although again not a perfect match (and the POTS, MCAS and Hashimoto's were separate diagnoses to the best of my knowledge).

Am just mentioning all of this in case it is helpful since I was a complete responder to high dose IVIG and Rituximab. I have never tried Rapamune.
 

andyguitar

Senior Member
Messages
1,054
Likes
2,484
Location
South east England
Anyone who is interested in the idea that an autoimmune disorder can effect a specific area of the brain and cause some very strange symptoms should consider this: Sudden onset OCD in children who had a Strep A throat infection. The autoimmune factor was that it caused an area of the brain-the Caudal-to swell up. When the correct treatment was given the swelling reduced and OCD went. Treatment was drugs and washing out the antibodies. Sounds like @Gingergrrl was given the diagnosis of ME/CFS by mistake.
 

ljimbo423

Senior Member
Messages
1,868
Likes
4,414
Location
United States, New Hampshire
Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis

J Immunol Res. 2017; 2017: 4835189.
Published online 2017 Aug 30.

Abstract
Characterization and understanding of gut microbiota has recently increased representing a wide research field, especially in autoimmune diseases. Gut microbiota is the major source of microbes which might exert beneficial as well as pathogenic effects on human health. Intestinal microbiome's role as mediator of inflammation has only recently emerged.

Microbiota has been observed to differ in subjects with early rheumatoid arthritis compared to controls, and this finding has commanded this study as a possible autoimmune process. Studies with intestinal microbiota have shown that rheumatoid arthritis is characterized by an expansion and/or decrease of bacterial groups as compared to controls.

In this review, we present evidence linking intestinal dysbiosis with the autoimmune mechanisms involved in the development of rheumatoid arthritis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602494/
 

Gingergrrl

Senior Member
Messages
14,255
Likes
42,578
Sudden onset OCD in children who had a Strep A throat infection.
This syndrome (Strep causing OCD, and often psychosis with violent behavior toward self or others in children with NO prior psych history, is called "PANDAS"). I watched a documentary about this about a year ago (I think on YouTube) but sadly I do not remember what the film was called. What struck me was that these children were in different countries, every single last one of them was initially misdiagnosed by multiple doctors, and many of them got vastly better with IVIG. I cannot for the life of me remember if any of them also got Rituximab (and I think a few of them did) but I am not certain of this like I am with the IVIG.

Sounds like @Gingergrrl was given the diagnosis of ME/CFS by mistake.
My journey to this point (2013 to 2019) was long and complex, as I know it is with all of us! I was given the initial "CFS" diagnosis by my former GP out of pure ignorance and laziness. The term "ME" is not used in the US, only "CFS", which is why I am using it here. My former GP told me that I had "CFS" and that there was no treatment and recommended "counseling". I told her I was an LCSW/therapist myself and if counseling could cure my medical problems, it would have been a miracle, but I knew they were medical.

In spite of this I saw a psychiatrist and he fully assessed me and determined that I was not depressed, and that it was obvious I had a medical problem just from my super low BP (80/50 which dropped further when I walked, plus extreme tachycardia, and all kinds of abnormalities on blood work). He also diagnosed me with "CFS" which he considered a medical issue and not psychiatric. He referred me to an Endo who immediately figured out that I had both Hashimoto's and POTS (which were both 100% correct diagnoses) but even he felt that more was going on and that it was "CFS".

So with three doctors of different disciplines giving me a "CFS" diagnosis (and it made sense b/c it was post-viral following severe Mono/EBV just 10-months earlier) I believed it to be correct. Ironically the first doctor who said, "I don't think you have ME/CFS" was an ME/CFS specialist who is still my main doctor today. He said that I was one of the sickest patients that he had, and he did not yet know why, but he did not think it was ME/CFS (even though I had sky high EBV titers, very low NK cell functioning, etc, which matched his other patients).

Just a thought.... as there maybe a question mark over @Gingergrrl diagnosis of ME/CFS could it be possible that patients that have been treated with Rituximab successfully did'nt have ME/CFS ? And vice versa?
I have this same thought all the time and for me there are three possibilities:

1) The people who got better from Rituximab (like me) never had CFS to begin with.

2) The people who got better from Rituximab had both CFS and a separate co-morbid autoimmune disease (which may or may not be diagnosed).

3) CFS (or at least a sub-set of it) is autoimmune and the people in that CFS sub-set got better from Ritux.

To bring this back to RA (the thread topic), there are people with 100% rock solid diagnoses of RA who do NOT improve with Ritux and others with RA who achieve complete remission. So being a responder to Ritux (or any med) does not in and of itself confirm a diagnosis.

But IMO, those who respond, have B-cell driven autoimmunity at the core of their illness. What I don't understand is how Fluge & Mella misdiagnosed so many people as having ME/CFS (using research criteria, not using zero criteria like my former GP)? Fluge & Mella had responders in their Ritux study (even if not statistically significant) and I want to learn more about that group of people and what diagnoses they had? Were they ALL misdiagnosed with ME/CFS? This seems strange to me. I would love to know exactly how I matched up with Fluge & Mella's responders (all I know so far is that we all had a positive ANA titer, some positive Cell Trend autoantibodies, and anti-thyroid antibodies like TPO).

I am very interested in this b/c most likely there is going to be a case study published about my case in a medical journal (not about ME/CFS vs. how these treatments are successfully used for a variety of autoimmune diagnoses like Autoimmune POTS, MCAS, LEMS, etc) and I am also very interested b/c literally no one knows if my remission is temporary or permanent. I am continuing Ritux at a 5-month interval w/a goal to stretch it out to a 6-month interval. I am very fearful (still) of this remission not being permanent and being back in a wheelchair, with severe POTS & muscle weakness, unable to walk or breathe again, and being allergic/anaphylaxis to food again.
 
Last edited:

andyguitar

Senior Member
Messages
1,054
Likes
2,484
Location
South east England
Thanks for putting all that info up @Gingergrrl it's both interesting and helpful. So as not to hijack this thread I will just say this: I think it is very probable that those who are reported to have got better from Rituximab did not have CFS. Fortunate there was a clinical trial that showed it did'nt work. I wonder how many other commonly used treatments that are supposed to work but have not been subject to clinical trial are usless- and potentially harmful.
 
Last edited:

Gingergrrl

Senior Member
Messages
14,255
Likes
42,578
Thanks for putting all that info up @Gingergrrl it's both interesting and helpful. So as not to hijack this thread I will just say this:
I just replied to your PM and also do not want to take this thread off track (which is my specialty... o_O)
 

wigglethemouse

Senior Member
Messages
466
Likes
1,182
I am very interested in this b/c most likely there is going to be a case study published about my case in a medical journal (not about ME/CFS vs. how these treatments are successfully used for a variety of autoimmune diagnoses like Autoimmune POTS, MCAS, LEMS, etc)
Oooooooooo, this must be incredibly exciting for you. I think case studies are a neglected area in ME and CFS and will help the field move forward to help future cases look for signs of things that can be treated with known proven medical therapies.
 

Gingergrrl

Senior Member
Messages
14,255
Likes
42,578
Oooooooooo, this must be incredibly exciting for you. I think case studies are a neglected area in ME and CFS and will help the field move forward to help future cases look for signs of things that can be treated with known proven medical therapies.
It's not 100% definite yet (so I probably should have kept my big mouth shut :rolleyes:) but the researchers who want to do this believe that my case will help a lot of people. They said it will spur additional research and will help more patients to get access to my treatments b/c it will be further evidence that they work in autoimmune cases of POTS and other autoimmune mediated cases where these treatments are denied.
 
Messages
31
Likes
115
@Gingergrrl Thank you!

It's not 100% definite yet (so I probably should have kept my big mouth shut :rolleyes:) but the researchers who want to do this believe that my case will help a lot of people. They said it will spur additional research and will help more patients to get access to my treatments b/c it will be further evidence that they work in autoimmune cases of POTS and other autoimmune mediated cases where these treatments are denied.
Awesome news - please keep us posted:)
Imho there are some patients in the CFS cohort, that probably improve with immunosuppressive medication because they developed some kind of autoimmunity problem and like Gingergrrl said, even if you have RA or other immune diseases - this does not mean that you respond to rituximab treatment.

@andyguitar I think it is probably quite difficult to distinguish CFS and AI conditions completely (at least for now) - so I think there will probably always be some kind of overlap as long as we do not have valid biomarkers.


Nope, no monitoring of blood levels of rapamune. Nor has it been suggested by my docs, but maybe I'm the one who needs to do the suggesting since I'm the one who requested it.

For the last 6+ months I have been fasting for 14 - 15 hours each day (well, mostly night) but haven't really noticed any effect, but I'm banking on long term benefits. My body seems to need lots of protein, and I minimize carbs, but yeah, keeping muscle and being inactive is a challenge.

Fwiw, in November I switched to Truvada for the Tenofovir for its potential impact on B cells. Curiously, I started to become hyperthyroid (according to tests) and have since lowered my dessicated thyroid (But I also have an empty sella and that could be messing my endocrine.) and my liver enzymes (ALT and AST) became elevated.
@ScottTriGuy
It seems the blood monitoring with sirolimus is a European thing according to this review and that is where I am based.;)
https://www.ncbi.nlm.nih.gov/pubmed/16029064

"This review seeks to apply a decision-making algorithm to establish whether clinical pharmacokinetic monitoring (CPM) of sirolimus (rapamycin) in solid organ transplantation is indicated in specific patient populations. The need for CPM of sirolimus, although a regulatory requirement in Europe, has not yet been firmly established in North America and other parts of the world."

I would also bank on long term benefits, but maybe you could integrate some lower protein, lower calorie days every few months - if you'd like to maximize the effect and only if this is possible for you? Caloric restriction or so called fasting mimicing diets can be quite a burden - especially if you have endocrine issues - do you have empty sella syndrome also? (Sorry if I am being too curious or if this is off topic...)

But of course the rapamune should have a more profound effect - please keep us posted how you are doing with the higher dose.:angel:
 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,285
Likes
5,208
Location
Toronto, Canada
@ScottTriGuy
It seems the blood monitoring with sirolimus is a European thing according to this review and that is where I am based.;)
https://www.ncbi.nlm.nih.gov/pubmed/16029064

"This review seeks to apply a decision-making algorithm to establish whether clinical pharmacokinetic monitoring (CPM) of sirolimus (rapamycin) in solid organ transplantation is indicated in specific patient populations. The need for CPM of sirolimus, although a regulatory requirement in Europe, has not yet been firmly established in North America and other parts of the world."

I would also bank on long term benefits, but maybe you could integrate some lower protein, lower calorie days every few months - if you'd like to maximize the effect and only if this is possible for you? Caloric restriction or so called fasting mimicing diets can be quite a burden - especially if you have endocrine issues - do you have empty sella syndrome also? (Sorry if I am being too curious or if this is off topic...)

But of course the rapamune should have a more profound effect - please keep us posted how you are doing with the higher dose.:angel:

Thanks for the monitoring info.

Yes, I have empty sella syndrome.

I think this is my 4th continuous day on Rapamune and the seborhheic dermatitis on my face and scalp is so much better. This also happened when I initially began.

So far I have not noticed a boost in exertion tolerance, but don't expect that for a few weeks.

Are you taking, or thinking of taking, Rapamune?
 
Messages
31
Likes
115
Thanks for the monitoring info.

Yes, I have empty sella syndrome.

I think this is my 4th continuous day on Rapamune and the seborhheic dermatitis on my face and scalp is so much better. This also happened when I initially began.

So far I have not noticed a boost in exertion tolerance, but don't expect that for a few weeks.

Are you taking, or thinking of taking, Rapamune?
@ScottTriGuy You are very welcome. :)
No, I am not taking rapamune, but I am also on an immunosupressant b/c I do have an AI disease, too. I can also relate to the endocrine issues.

The problem ist I now developed leucopenia with the medication and we probably have to switch (again). Sadly rituximab and other drugs are really considered last "last resort choices" and mostly the typical and cheaper drugs like imuran, methotrexate etc are used. Even if I wanted I probably would not have access to mTOR inhibitors like rapamune b/c it would be considered highly experimental for patients without having endured an organ transplant and most doctors really do not like to use "off-label" treatments - even if one failed all "on-label" medications.

May I ask what diagnosis you (or your doctor) are treating with rapamune?
You can also contact me via PM in case you do not feel comfortable sharing this openly on the boards...

I have to admit, I am still not being used to share my thoughts and illness(es) on the forum, but I am very happy that I received such a kind welcome here so far:angel::angel::angel:

Thank you everybody!