Martin aka Paused and H.E.L.P treatment

[SWAlexander]

Thank you! I think I have to make contact with an endocrinologist

Make sure you get a ACTH test and aldosteron test as well.

 

[Keats]

Jaeger called me today. I have severe epithelial damages and a severe form of EBV reactivation with a high viral load. Interesting that Red Labs could not detect viral DNA, but it showed many strange things.

And yes, I have a high amount of fat droplets. She thinks the infection is causing all this. What I immediately thought is that enteroviruses can cause all this (titer 1:640).

My LDL-Cholesterol is high. My potassium very low.

She thinks what would help me most is remove the lipids and fight the infection. But it could need apheresis for up to one year (she doesn’t want to earn money with it; she contacted another clinic which isn’t that far for me. Furthermore she will contact a lawyer because we will have to fight for my insurance to pay the costs.

Two final notes. Greetings to me from William Weir (was surprised he kept me in mind) and my interview will be aired on tv soon. This then potentially means a run by ME patients on apheresis

 

[Keats]

Thank you so much Martin, for dealing with all of this and reporting it to us. I’m sure that the thorough testing you are having will provide a lot of data for Dr Jaeger and Co to work with. Fingers so firmly crossed for you.

 

[SlamDancin]

@Martin aka paused||M.E. Hey Martin thanks so much for all this data. I’m personally invested in your story, especially, as I have always had high cholesterol as well. My question right now is how was the EBV reactivation diagnosed? My blood tests were pretty mild re: viruses, I had some notable HHV7 and Varicella titers but none of my doctors at the time were very impressed. I know it’s n=1 but it does seem like if you just look in the right place you find viral load in ME/CFS but for whatever reason it doesn’t always show up in larger studies

 

[HealingFalcon]

Jaeger called me today. I have severe epithelial damages and a severe form of EBV reactivation with a high viral load. Interesting that Red Labs could not detect viral DNA, but it showed many strange things.

And yes, I have a high amount of fat droplets. She thinks the infection is causing all this. What I immediately thought is that enteroviruses can cause all this (titer 1:640).

My LDL-Cholesterol is high. My potassium very low.

She thinks what would help me most is remove the lipids and fight the infection.

(...) and my interview will be aired on tv soon. This then potentially means a run by ME patients on apheresis

Thanks for your update Martin!
This sounds very exiting... maybe you have some answers or ideas to the following questions:

Do you know what Dr. Jäger thinks causes your epithelial damage and why does she think it leads to your ME/CFS? What could be the mechanism behind it? How does it lead to PEM?

Also, how should HELP apheresis alleviate the epithelial damage and why would it take so long?

I myself had one HELP apheresis but it crashed me a lot...It did not look like I had loads of clots in the filter either.

High D-Dimer, high antiplasmin, high triglycerides, high LDL, high Cox B4 and B5 and A7 (1:640 or higher), probably chronic VZ and CMV as well as Toxoplasmosis (no DNA, only very high titers and high LTT), various Celltrend autoantibodies, high Angiotensin.

I hope Dr. Jäger is really onto something as I am still afraid it is just another hypothesis that may be true for some but only a minority ...

 

[bensmith]

@HealingFalcon heres hoping to a majority.

 

[GlassCannonLife]

@Martin aka paused||M.E. Interesting! Have you not had EBV tested in the past? Someone already asked but yes it would be great to know how they tested vs what you did in the past!

Have you never trialled valtrex?

 

[Akasha]

And yes, I have a high amount of fat droplets. She thinks the infection is causing all this.

I've been looking around and found a book chapter that talks about the Rotaviruses (RV) link with lipid droplets (LD). It summarizes a lot of pathogens that also produce LD.

Here are some excerpts of interest:

Viroplasms interact with and possibly trigger the formation of LDs, inducing and recruiting them during the replication cycle (Cheung et al., 2010; Saxena et al., 2015).

Rotaviruses have joined the growing list of viruses and microbes that interact with LDs during their replication and depend on cellular lipid homoeostasis, including hepatitis C virus (Miyanari et al., 2007; Boulant et al., 2007; Shavinskaya et al., 2007; Salloum et al., 2013; Paul et al., 2014; Liefhebber et al., 2014; Shahidi et al., 2014; Filipe et al., 2015), dengue virus (Samsa et al., 2009; Jain et al., 2014; Soto-Acosta et al., 2014), GB virus B (Hope et al., 2002), bunyavirus (Wu et al., 2014) and the intracellular parasites Chlamydia (Kumar et al., 2006), Mycobacterium tuberculosis (Daniel et al., 2011) and Mycobacterium leprae (Mattos et al., 2011). On a wider scale, FA biosynthesis has been recently recognized as being essential for the replication of a larger number of viruses such as enteroviruses, West Nile virus, human cytomegalovirus, Kaposi sarcoma associated herpes virus and Epstein Barr virus (Chukkapalli et al., 2012).

​

I think this is a similar process to the one found with microclots. A presumably persistent infection triggers the formation of lipid droplets (or microclots) and those provoke endothelial damage, responsible for the symptoms.

Thanks for the update @Martin aka paused||M.E. wishing you the best with this process. It looks like Dr. Jaeger was waiting to call you until she had news

PD: If someone is interested, the DOI of the book is https://doi.org/10.1016/B978-0-12-802241-2.00009-2

 

[Akasha]

An also:

Viruses from the Flaviviridae family, namely dengue virus (DENV), hepatitis C virus (HCV), West Nile virus (WNV), and Zika virus (ZIKV), interact with LDs to usurp the host lipid metabolism for their own viral replication and pathogenesis. In general, during Flaviviridae infections it is observed an increasing number of host intracellular LDs. Several viral proteins interact with LDs during different steps of the viral life cycle.

From: https://www.frontiersin.org/articles/10.3389/fmicb.2018.01951/full

 

[Marylib]

Thanks for the update @Martin aka paused||M.E. I hope this works out for you. I guess she was able to examine the epithelia of the cells that were removed by apharesis? For some reason I was thinking this procedure would require a biopsy to extract the tissue...

 

[junkcrap50]

I'd like to know how they tested for epithelial damage. Dr Carmen Scheibenbogen in some of her studies used a specialized, noninvasive test for endothelial health.

First, they used a non-invasive technique called “Peripheral Arterial Tonometry (PAT)” to measure changes in the “vascular tone”. During the test a blood pressure cuff reduces blood flows to the hand for five minutes. After the cuff is opened the amount of blood flowing to the fingers is measured.

The EndoPat test, which can be done in a doctor’s office, can be used to quickly assess risk factors for cardiovascular diseases such as heart failure, stroke, and pulmonary arterial hypertension.

In contrast to other cardiovascular tests, PAT assesses microvascular functioning; i.e. the functioning of the peripheral arterioles found just before the capillaries. These arterioles, which are lined with smooth muscles, are where most of the blood flow regulation occurs. If not enough nitric oxide (NO), a vasodilatory substance, is produced, the arterioles will not be able to dilate enough to let sufficient amounts of blood through to the capillaries which transmit nutrients to the tissues.

Source:https://www.healthrising.org/blog/2...-vessels-arterioles-chronic-fatigue-syndrome/

 

[GlassCannonLife]

@junkcrap50 @Marylib

I haven't looked in depth at the specifics but epithelial/endothelial damage can be assessed using a number of markers. Please see this paper for some information.

For example:

At each point, blood was collected for hyaluronan, syndecan-1, vascular cell adhesion molecule (VCAM-1), and von Willebrand factor (vWF), and a perused boundary region (PBR) measurement was performed.

The breakdown of the glycocalyx is a known phenomenon that occurs with this type of damage and has been studied a lot the context of organ transplant, critical care, etc. It is likely that they used some type of injury marker like this.

The PAT technique is interesting. I don't think it would be practical to take a tissue biopsy for this type of thing as the tissues are extremely fragile and extraction itself would likely cause damage.

I look forward to seeing Martin's report on the testing that was used, however, so we may hopefully try something similar on ourselves. If Dr Jaeger gave an indication as to what could be the cause of this aside from general high levels of oxidative stress, lack of activity, etc (all general ME/CFS factors), that would be also great to know.

 

[junkcrap50]

@junkcrap50 @Marylib

I haven't looked in depth at the specifics but epithelial/endothelial damage can be assessed using a number of markers. Please see this paper for some information.

For example:



The breakdown of the glycocalyx is a known phenomenon that occurs with this type of damage and has been studied a lot the context of organ transplant, critical care, etc. It is likely that they used some type of injury marker like this.

The PAT technique is interesting. I don't think it would be practical to take a tissue biopsy for this type of thing as the tissues are extremely fragile and extraction itself would likely cause damage.

I look forward to seeing Martin's report on the testing that was used, however, so we may hopefully try something similar on ourselves. If Dr Jaeger gave an indication as to what could be the cause of this aside from general high levels of oxidative stress, lack of activity, etc (all general ME/CFS factors), that would be also great to know.

Wow. Good info. Thanks!

But the PAT technique does not use a biopsy. It is non invasive. It's a blood pressure cuff and and special sensor on a finger pulse-type clip. It's just a very narrow medical device, so not very common. But a few cardiology and GP offices have it on their websites when I googled it online.

 

[GlassCannonLife]

Wow. Good info. Thanks!

But the PAT technique does not use a biopsy. It is non invasive. It's a blood pressure cuff and and special sensor on a finger pulse-type clip. It's just a very narrow medical device, so not very common. But a few cardiology and GP offices have it on their websites when I googled it online.

Sorry I was responding to @Marylib with the rest of that paragraph. Probably should have separated the sentences!

 

[Martin aka paused||M.E.]

Hi,

I’m sorry atm I’m in a bad flare and unable to answer all your questions.
Hope I will be able to come back to them soon.

 

[HealingFalcon]

[

I've been looking around and found a book chapter that talks about the Rotaviruses (RV) link with lipid droplets (LD). It summarizes a lot of pathogens that also produce LD.

Here are some excerpts of interest:

​

​

​

I think this is a similar process to the one found with microclots. A presumably persistent infection triggers the formation of lipid droplets (or microclots) and those provoke endothelial damage, responsible for the symptoms.

Thanks for the update @Martin aka paused||M.E. wishing you the best with this process. It looks like Dr. Jaeger was waiting to call you until she had news

PD: If someone is interested, the DOI of the book is https://doi.org/10.1016/B978-0-12-802241-2.00009-2

I am afraid it is quite complicated.

Other papers found that the increase in lipid droplets is not only regulated by the infection but also by the host and is necessary for a proper antiviral response:

"Following infection of cells with either RNA viruses (Zika, Dengue, Influenza A) or a DNA (Herpes Simplex Virus-1) virus, LDs were rapidly upregulated, and this response was also replicated following stimulation with viral mimic agonists. This upregulation of LDs following infection was transient, and interestingly, did not follow the well described homeostatic mechanism of LD upregulation, instead being controlled by EGFR. The cell's ability to mount an effective immune response was greatly diminished when inhibiting EGFR, thus inhibiting LD upregulation during infection, also leading to an increase in viral replication."
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8404386/

Maybe the upregulation of lipid droplets is not only virally generated for their replication but rather an essential part of our immune response as our immune system evolved around the increase in lipid droplets following infection.

Would be very interesting to know what Dr. Beate Jaeger thinks about this and why she believes the removal of lipid droplets would be beneficial and not detrimental to our antiviral capacity.
I crashed after my first help apheresis. Could it be that the removal of lipid droplets left me with no cytokines etc. which are not only directly removed but also indirectly via the reduction of lipid droplets to fight chronic infection?

Maybe HELP apheresis is still beneficial as it intervenes in the process of generating replication organelles and if this can be prevented we don't need as much antiviral capacities.
But still, I do wonder if it could be detrimental to remove the lipid droplets as it might impair the antiviral capacity which is probably already quite low in pwME...

"The accumulation of LDs has become a hallmark of infection, and is often thought to be virally driven; however, recent evidence is pointing to a role for the upregulation of LDs in the production of a successful immune response to viral infection. The fatty acids housed in LDs are also gaining interest due to the role that these lipid species play during viral infection, and their link to the synthesis of bioactive lipid mediators that have been found to have a very complex role in viral infection. This review explores the role of LDs and their subsequent lipid mediators during viral infections and poses a paradigm shift in thinking in the field, whereby LDs may play pivotal roles in protecting the host against viral infection."

https://academic.oup.com/femsre/article/45/4/fuaa066/6123723

 

[perrier]

[



I am afraid it is quite complicated.

Other papers found that the increase in lipid droplets is not only regulated by the infection but also by the host and is necessary for a proper antiviral response:

"Following infection of cells with either RNA viruses (Zika, Dengue, Influenza A) or a DNA (Herpes Simplex Virus-1) virus, LDs were rapidly upregulated, and this response was also replicated following stimulation with viral mimic agonists. This upregulation of LDs following infection was transient, and interestingly, did not follow the well described homeostatic mechanism of LD upregulation, instead being controlled by EGFR. The cell's ability to mount an effective immune response was greatly diminished when inhibiting EGFR, thus inhibiting LD upregulation during infection, also leading to an increase in viral replication."
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8404386/

Maybe the upregulation of lipid droplets is not only virally generated for their replication but rather an essential part of our immune response as our immune system evolved around the increase in lipid droplets following infection.

Would be very interesting to know what Dr. Beate Jaeger thinks about this and why she believes the removal of lipid droplets would be beneficial and not detrimental to our antiviral capacity.
I crashed after my first help apheresis. Could it be that the removal of lipid droplets left me with no cytokines etc. which are not only directly removed but also indirectly via the reduction of lipid droplets to fight chronic infection?

Maybe HELP apheresis is still beneficial as it intervenes in the process of generating replication organelles and if this can be prevented we don't need as much antiviral capacities.
But still, I do wonder if it could be detrimental to remove the lipid droplets as it might impair the antiviral capacity which is probably already quite low in pwME...

"The accumulation of LDs has become a hallmark of infection, and is often thought to be virally driven; however, recent evidence is pointing to a role for the upregulation of LDs in the production of a successful immune response to viral infection. The fatty acids housed in LDs are also gaining interest due to the role that these lipid species play during viral infection, and their link to the synthesis of bioactive lipid mediators that have been found to have a very complex role in viral infection. This review explores the role of LDs and their subsequent lipid mediators during viral infections and poses a paradigm shift in thinking in the field, whereby LDs may play pivotal roles in protecting the host against viral infection."

https://academic.oup.com/femsre/article/45/4/fuaa066/6123723

Interesting material. Thank you. My I ask how many of these HELP apheresis treatments you had? Would you say, there was no benefit, or some? And how severe was your crash? Thank you.

 

[HealingFalcon]

Interesting material. Thank you. My I ask how many of these HELP apheresis treatments you had? Would you say, there was no benefit, or some? And how severe was your crash? Thank you.

I only had one apheresis two month ago as the following crash left me permanently worse and I am not able to attent another appointment at the moment (I was already severe). There was no benefit at all but I would not expect a (huge) benefit as I only had one treatment...

 

[Martin aka paused||M.E.]

@HealingFalcon Jaeger told me that it would also reduce the viral load. But it could much time to eliminate EBV. So I want to discuss with her a combined approach with high dose Valtrex and IFN-lambda to simultaneously remove enteroviruses. I think it’s the main culprit that leads to all these problems

 

[Akasha]

The accumulation of LDs has become a hallmark of infection, and is often thought to be virally driven; however, recent evidence is pointing to a role for the upregulation of LDs in the production of a successful immune response to viral infection

Interesting...I thought viruses used LDS to replicate

If this hypothesis turns to be true, it looks like treatment would need a two-dimensional approach, apheresis and antivirals.
Using apheresis to remove what produces endothelial damage and as many viral particles as possible while taking antivirals to control the infection.

I was never fond of the persistent viral infection theory, but I'm starting to change my mind.