Mono Virus Discovery - Implications for ME/CFS?

[Cort]

Cincinnati Children's Hospital just patented a system for transcription factor modification to treat autoimmune diseases. Here is a youtube video about the problem:

Can someone show this to Dr Davis et all?

In a recent talk Ron was musing about what EBV did during its initial infection in many ME/CFS patients. I think he will be glad to see this paper

 

[Cort]

@Janet Dafoe (Rose49) any way to reach out to these researchers who seem to be searching for collaborations?

What an opportunity not only to learn about ME/CFS but to get ME/CFS included with all these other autoimmune diseases! This is a huge opportunity! Thanks for mentioning that.

 

[Gingergrrl]

In a recent talk Ron was musing about what EBV did during its initial infection in many ME/CFS patients. I think he will be glad to see this paper

What an opportunity not only to learn about ME/CFS but to get ME/CFS included with all these other autoimmune diseases! This is a huge opportunity! Thanks for mentioning that.

This is great and I am glad that Dr. Davis will be alerted to this research on EBV and autoimmunity. I assume he already knows about it but I was not sure if this particular research had a new twist or focus that could be relevant. Thanks for alerting him!

 

[Pondering]

So if I understand this (and I may not which is why I am posting)... they have found that EBV has a protein (EBNA2) that impacts the regulation of certain genes. It does this by working through the human transcription factors.

When they then in turn looked at the genes impacted by EBNA2 they found that these genes were in turn associated with a group of diseases. They looked at lupus and other autoimmune diseases as those are the one that they had expertise in.

So, if EBV is in fact having a similar impact in ME/CFS we would expect to see the genes that have been found to be upregulated in past studies of ME/CFS patients to also be in those effected by EBNA2.

A quick glance at previous research shows this...

"A comprehensive gene signature of non-psychiatric patients with CFS has been generated by a whole-genome microarray assay. The microarray data presented here illustrates differences in gene expression across the human genome between post-infectious, non-psychiatric male patients with CFS and healthy controls. Analysis of the gene signature of CFS suggests that three significant pathways are altered in patients: oxidative stress, apoptosis and viral-like immune modulation. Previously, Gu et al. [41] performed a 588-gene microarray whereby patients with spondyloarthropathy, rheumatoid arthritis and psoriatic arthritis were compared to normal healthy subjects. Of interest was their finding that expression of CXCR4 was unexpectedly high among all arthritis subjects. This gene encodes a CXC chemokine receptor that is specific for one ligand (stromal cell-derived factor-1), and CXCR4 is known to act with CD4 protein to support HIV entry into cells. DNA microarray studies by Watanabe and co-workers [42] demonstrated significant up-regulation of the CXCR6 motif in ulcerative colitis patients, whilst other work has indicated that the CXCL12/CXCR4 interaction is involved in several inflammatory conditions, including inflammatory bowel disease [43]. As a result, the finding from our study (that CXCR4 was significantly up-regulated in male CFS patients) indicates that this gene may not be specific to CFS. It is noted, however, that in the CFS studies by Kerr et al. (44, 45), CXCR4 was also up-regulated." - https://bmcmedgenomics.biomedcentral.com/articles/10.1186/1755-8794-2-38

The list of diseases seems to match what was found... Hopefully the genes match?

 

[Pondering]

Hmm... looking at their patent they list the transcription factors that they are saying that EBV works with.

This article helpfully lists the transcription factors that they found associated with ME/CFS https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02405.x

"The increase of so many genes might indicate that upstream transcription factors common to all of these genes are dysregulated and control these downstream genes in a pathological fashion in CFS. Interestingly, all of the genes measured here are interconnected by the transcription factors CREB, GR‐alpha (part of NR3C1, the glucocorticoid receptor) and NF‐Kappa B1."

So.. a quick look in the patent finds that they feel that EBV impacts CREB and NR3C1. They don't mention NF-Kappa B1 directly but one of their cited articles does.

Ersing, I., Bernhardt, K. & Gewurz, B. E. NF-kappaB and IRF7 pathway activation by Epstein-Barr virus

All in all if I understand the science correctly (which I very well might not), it seems like what they found with EBV may be relevant.

 

[Learner1]

Yes, but other researchers have identified different groups, like the Lights, Neil McGregor, and the group at Stanford.

What we need is a model of all the potential suspects, along with how they impact metabolomics, and then an AI program that can read our genetic info and metabolomics results and suggest interventions to compensate for what's not working... We are not all the same and there are likely multiple paths to our symptoms.

...or maybe there's one magic pill that hasn't been found yet...

 

[Learner1]

Or maybe we need this:

https://www.google.com/amp/s/www.en...oneer-make-at-home-test-that-detects-disease/

From the article:

Biotech company Mammoth Biosciences is working on a simple, portable test that would give everyone, from healthcare professionals to just people at home, the ability to detect various diseases, infections and cancers quickly and easily.

The test would use CRISPR to determine which bacteria, viruses or genetic mutations were present in a person's blood, saliva or urine and a companion app would inform users about what was detected.

"Imagine a world where you could test for the flu right from your living room and determine the exact strain you've been infected with, or rapidly screen for the early warning signs of cancer," Mammoth CEO Trevor Martin said in a statement. "That's what we're aiming to do at Mammoth -- bring affordable testing to everyone."
...
An MIT lab also credited with pioneering CRISPR technology is working on a similar test. Recent research from the scientists showed how a simple paper strip loaded with CRISPR enzymes can detect viruses like Zika and dengue in human samples

 

[FMMM1]

As others have said, I assume we need researchers to prove cause and effect; however, given the list of diseases, that research may deliverable.

1) can you definitively tell whether you have been exposed to EBV?
I think Cort Johnson wrote an article(s) highlighting Ian Lipkin's track work on identifying past exposure to viruses in ME/CFS. Perhaps that data has already established an increased risk of developing ME/CFS, lupus etc. following exposure to EBV or other virus's.
2) Can you determine your current (B-cell) gene expression i.e. after exposure to EBV (or other virus of interest)?
3) Can you determine your original (B-cell) gene expression i.e. before exposure to EBV (or other virus of interest)?
4) Can you re-set your (B-cell) gene expression i.e. to the position before ME/CFS? E.g. by zapping your B-cells and then re-populating using a bone marrow transplant? Or by modulating the expression of the (B-cell) genes, i.e. to replicate the original setting? If so then does this cure/mitigate the effect of the disease?

 

[Gingergrrl]

Brilliant post above @FMMM1 and it is basically what I am in the process of trying to do. I was definitively exposed to EBV (and have no idea about gene expression) but am trying to re-set my B-cells to pre-EBV and pre-Autoantibodies through high dose IVIG and Rituximab. My B cells have been at zero for about nine months with great symptom improvement (and will stay that way for two more doses of Ritux) and then we will find out what happens when they start to grow back

 

[FMMM1]

My ME/CFS doctor had explained to me a year ago that my autoimmune issues, including celiac, POTS, and MCAS were likely triggered by my EBV.

I read through the patent, and am a little concerned for what it means. It was developed with federal funding and seems to be patenting the use of any dose of any of the Column C treatments, many of which my doctors have already prescribed for me, for use on patients with any of these EBV causes autoimmune issues...what will the impact of this be? Treatment we can't afford that someone makes millions off of?

Yea. Drugs are only patented for a limited period of time. I wonder if they are used (after the patent has expired) for a disease they were not originally licensed for (possibly ME/CFS) if this can be used to extend the patient? Check this out "Patent cliff and strategic switch: exploring strategic design possibilities in the pharmaceutical industry"; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899342/.

I think there may be two questions i.e. what happens when the patient expires and what happens when a licensed drug (e.g.antiviral) is used in a new way.

All controlled by your politicians/government so check it out with them.

 

[Wally]

It is my understanding that there are some parallel research projects that will be going on soon re ME/CFS and EBV. I am not able to provide any other information about this research at this time, but I just wanted people to know that the possibility of EBV being a major player in this illness is still very much on the research table.

No guarantees whether this research will provide answers, but I am more optimistic than I have been in a long time that the underlying premise makes sense. Perhaps Dr. Lerner understood more about this illness than he was given credit for.

If the EBV carrot still interests people, I recommend that you look at research from other countries involving some of the illnesses listed in the video. Very interesting that this type of research does not directly involve drugs, but proposes other methods to try reset the body at a cellular level. Also interesting how these methods may also have been looked at for HIV. Could it be that the story of retroviruses and herpesviruses may still be in play? Sometimes when tackling things head on you find yourself up against a wall that seems insurmountable. If you can’t get over or around the wall, you might need to bide your time to quietly and stealthily dig a tunnel under the wall to find a way to the other side.

 

[Gingergrrl]

I think there may be two questions i.e. what happens when the patient expires and what happens when a licensed drug (e.g.antiviral) is used in a new way. All controlled by your politicians/government so check it out with them.

I think you mean when the patent expires, not when the patient expires (I hope... ) and just a Freudian slip LOL. In the US, meds can be prescribed off-label regardless if the patent has expired if the doctor chooses to do so. If the patient can pay privately, it is a non-issue. If not, then the doctor has to make a good case to the insurance company re: why they are prescribing that med off-label vs. something else (most likely cheaper). And if the off-label med happens to be the cheaper option, then the insurance will not even care.

I am not able to provide any other information about this research at this time, but I just wanted people to know that the possibility of EBV being a major player in this illness is still very much on the research table.

I have always believed (well since I got sick myself, before that I knew nothing), that EBV was one of the major players in ME/CFS, in autoimmunity, in many cancers, etc. It is not the benign virus that many people think just causes Mono.

 

[mariovitali]

The technology and idea behind this is quite interesting however not everyone got ME/CFS from EBV or even a Virus. However there are many patients who got ME/CFS from EBV.

Looking forward to learning more.

 

[Gingergrrl]

The technology and idea behind this is quite interesting however not everyone got ME/CFS from EBV or even a Virus. However there are many patients who got ME/CFS from EBV.

I agree that it will only pertain to a sub-set of people (but I believe that is the case with just about everything).

 

[babeng]

Brilliant post above @FMMM1 and it is basically what I am in the process of trying to do. I was definitively exposed to EBV (and have no idea about gene expression) but am trying to re-set my B-cells to pre-EBV and pre-Autoantibodies through high dose IVIG and Rituximab. My B cells have been at zero for about nine months with great symptom improvement (and will stay that way for two more doses of Ritux) and then we will find out what happens when they start to grow back

Hi. Can I ask the reason for doing IVIG as well as Rituximab? My medical knowledge is pretty limited, but is the reason to have better antibodies to fight of possible EBV once the B-cells grow back, and therefore hopefully prevent a relapse? Or do you take the IVIG to somehow increase the chances of response from the rituximab? And if so, how?

The reason I'm asking is that I am a non-responder from rituximab, and I'm considering trying IMIG as a stand alone therapy. Just curious what your reasons are for taking them both at the same time ..

Happy to hear you have improved from the treatment!
All the best

 

[Learner1]

Hi. Can I ask the reason for doing IVIG as well as Rituximab? My medical knowledge is pretty limited, but is the reason to have better antibodies to fight of possible EBV once the B-cells grow back, and therefore hopefully prevent a relapse? Or do you take the IVIG to somehow increase the chances of response from the rituximab? And if so, how?

I am on IVIG only but may try Rituximab at some point if my doctor and I decide I might be a responder and the risks aren't too great.

Though I had multiple chronic infections, including Epstein Barr and low Immunoglobulins, which is a typical scenario for someone on IVIG for immunodeficiency, a major reason I am on IVIG is to try to attack/reverse my autoimmune issues.

My doctor has me on double the dose of patients with immunodeficiency. My side effects are more significant than those of immunodeficiency patients and all my doctors believe it's due to my autoimmunity and the fight it provokes in my immune system, in layman's terms.

At this point, after 9 months, my infections are better (which would be a prerequisite for Rituximab) and my autoimmune POTS has improved, though its far from gone. My doctor wants to increase the dose or frequency of the IVIG. I have tried backing off the frequency twice, but I got sicker until I got the IVIG, so I know its helping.

The reason for trying the IVIG would be to wipe out my B cells with any lingering EBV and the various autoimmune antibodies I've acquired, to clean house, so to speak. If I did it with an ongoing infection, I'd lose the antibodies to it and more would be produced, but the infection could be more dangerous.

Doing IVIG with Rituximab gives the body some protection while Rituximab has wiped out the B cells.

The risk to Rituximab is that you never make B cells again, but as the immunologist who told me that said, if you're already immunodeficiency and getting IVIG for the rest of your life, it wouldn't be any different...

This is my understanding now, but I will be discussing all very carefully with my doctor who has used both on other patients.

@Gingergrrl will likely give you a different view, but her situation is/was very different than mine, so you'll have to see what fits you.

Do you have any chronic infections?

The reason I'm asking is that I am a non-responder from rituximab, and I'm considering trying IMIG as a stand alone therapy. Just curious what your reasons are for taking them both at the same time ..

Happy to hear you have improved from the treatment!
All the best

Though its been an effort, I feel that IVIG has greatly helped me. Good luck!

 

[Gingergrrl]

Can I ask the reason for doing IVIG as well as Rituximab? My medical knowledge is pretty limited

My medical knowledge is limited, too, so this explanation is from my own perspective and research (and I am not quoting my doctor here). We identified that I had several autoantibodies (eleven) and my main doctor felt they were the cause of my muscle weakness, breathing weakness, POTS, etc. He felt that high dose IVIG was effective in autoimmunity and my mast cell doctor gives it to his MCAS patients and said that it even put some into remission. So when both doctors agreed that high dose IVIG was the best treatment plan for me (in 2016) we started it (for autoimmunity, not for immune deficiency).

It put my MCAS into remission and greatly improved my muscle weakness. Since I was a responder to high dose IVIG, we had more proof (for ourselves and for my insurance company) that I had a good chance of being a responder to Rituximab. We felt that IVIG was more like a band-aid in knocking down the (fully grown) autoantibodies vs. Rituximab would get to the root cause/source by killing the B-cells and stopping the autoantibodies at production level. We had a solid case for my insurance company and we got it approved (which was not easy).

So I did a full year of IVIG first (started July 2016) and then started this course of Ritux in July 2017. My 5th Ritux infusion is tomorrow. The IVIG had plateau'd and my additional improvements (now being able to walk short distances without wheelchair and drive my car again, etc) are all from the Rituximab. They work in conjunction or synergistically and were a very effective combination in my case. IVIG also helps keep your immune system stronger while you have no B-cells (although this was not the reason that I did it).

The reason I'm asking is that I am a non-responder from rituximab, and I'm considering trying IMIG as a stand alone therapy. Just curious what your reasons are for taking them both at the same time ..

I assume when you said "IMIG" that you meant "IVIG". I hope I explained above so it answered your questions.

Happy to hear you have improved from the treatment!

Thank you so much!

@Gingergrrl will likely give you a different view, but her situation is/was very different than mine, so you'll have to see what fits you.

I think we are different b/c I had no active infections at the point that I started IVIG & Rituximab and for me it was 100% for autoimmunity. I would not have done Ritux with active infections and was tested for many things first just to be safe. Autoantibody tests are no longer accurate once you are doing IVIG, but you can still do PCR testing.

 

[babeng]

Do you have any chronic infections?

First of all, thanks for your reply. I do not have any chronic infections, at least symptom wise. But as many others my blood work do show signs or hints of ongoing infections. I'm aware of some people with weak immune systems that struggle with ongoing infections that almost recover completely with gammaglobulins, and even though I'm not on one of those cases, I figure it's worth a shot.

I assume when you said "IMIG" that you meant "IVIG". I hope I explained above so it answered your questions.

Thanks for your response as well. I now understand the logic behind doing bot the IVIG and Rituximab. I did in fact mean IMIG, as intramuscular is the standard - and from what I know only way - for CFS patients to get gammaglobulins where I'm from...

Autoantibody tests are no longer accurate once you are doing IVIG

Does this mean forever? Or only when you are on it, and some time period after?

 

[Learner1]

First of all, thanks for your reply. I do not have any chronic infections, at least symptom wise. But as many others my blood work do show signs or hints of ongoing infections. I'm aware of some people with weak immune systems that struggle with ongoing infections that almost recover completely with gammaglobulins, and even though I'm not on one of those cases, I figure it's worth a shot.

Er.... ME/CFS can be a symptom. Have you had testing for things like Epstein Barr, cytomegalovirus, HHV6, cocksackie virus, atypical pneumonias, etc.?

Finding any these and treating them can help a lot. Many of us had no real sickness symptoms yet these infections were doing a great deal of damage. And once entrenched, they are unlikely to go away on their own without an antiviral, antibiotic, ozone, or other treatment.

Thanks for your response as well. I now understand the logic behind doing bot the IVIG and Rituximab. I did in fact mean IMIG, as intramuscular is the standard - and from what I know only way - for CFS patients to get gammaglobulins where I'm from...

The terminology in the US is SCIG, for subcutaneous IG. My doctor said the fosevim on is too high to do SCIG, and given the side effects I've experienced, doing it that way would make me sick all the time, not just the few days after IVIG, with the rest of my life being more normal as it is now.

Does this mean forever? Or only when you are on it, and some time period after?

I believe its while on it and for some time after.

 

[Gingergrrl]

Thanks for your response as well. I now understand the logic behind doing bot the IVIG and Rituximab. I did in fact mean IMIG, as intramuscular is the standard - and from what I know only way - for CFS patients to get gammaglobulins where I'm from...

I have never heard of IMIG, but if it is another name for SCIG, it would be next to impossible to do high dose for autoimmunity in that form. SCIG is usually given in a low dose for immune deficiency.

Does this mean forever? Or only when you are on it, and some time period after?

My mast cell doctor (who is an immunologist) said it takes about eight weeks after IVIG is totally done although this is just an approximation.