Article: Chronic Fatigue Syndrome (CFS) associated with Epstein-Barr virus infection.

[Manuel]

@Learner1
I've been looking at the LabCorp catalog you mentioned and I can't find the proof I'm saying. The closest thing I've found is this. They test CD8+ HLA-DR+ (are activated CD8 lymphocytes), which is a subpopulation of CD3+ HLA-DR+ (the activated t-lymphocytes I mean). If you look at the reference values of CD8+ HLA-DR+(activated CD8 lymphocytes) they are different from CD3+ CD8+(activated and non-activated CD8 lymphocytes, i.e. all CD8). This is what I mean, CD3+ values are different from CD3+ HLA-DR+, since CD3+ HLA-DR+ are only activated and CD3+ are activated and not activated.

The documents you enclosed I'll take a good look at them tomorrow because I can't today.

 

[Learner1]

@Learner1
I've been looking at the LabCorp catalog you mentioned and I can't find the proof I'm saying. The closest thing I've found is this. They test CD8+ HLA-DR+ (are activated CD8 lymphocytes), which is a subpopulation of CD3+ HLA-DR+ (the activated t-lymphocytes I mean). If you look at the reference values of CD8+ HLA-DR+(activated CD8 lymphocytes) they are different from CD3+ CD8+(activated and non-activated CD8 lymphocytes, i.e. all CD8). This is what I mean, CD3+ values are different from CD3+ HLA-DR+, since CD3+ HLA-DR+ are only activated and CD3+ are activated and not activated.

The documents you enclosed I'll take a good look at them tomorrow because I can't today.

I think if you want us patients to give you good information, we need a simple hit list, why you want each, definitions of each, and alternate nomenclatures. I know you think you've explained it, but it needs to be dumbed down further.

We are at the mercy of the whims of our doctors (and our insurance) and unless we can explain why we need a test, we have little chance of getting it done.

As for genetic testing, here's an overview of genetic testing covered by insurance in the US. In Table 5, they list the tests most commonly covered - HLA is listed, but only DQ for celiac disease, as I had done. I don't know of a cheap way of getting the DR variants done, but would love to know, especially for patoents with BCBS.

https://www.medscape.com/viewarticle/804131_3

 

[Berzerkerina]

Manuel, what do you think of Rituximab ?it would be the cure for people with chronic ebv

 

[Learner1]

Rituximab shouldn't be given to people with active infections, should it?

 

[Manuel]

@Berzerkerina @Learner1
About rituximab I think that it should first be given together with antivirals to prevent herpesvirus reactivations by immunosuppressing with that treatment. But rituximab only goes against cells that express CD20. The expression of CD20 includes from the pre-B cell stage to the B cell memory stage. In addition, CD20 is expressed in more than 90% of non-Hodgkin's lymphoma B cells, but is not detected in stem cells, pro-B or plasma cells. Thus, any targeted therapy against CD20 will not act on plasma cells. In addition, to see if this treatment really works, CFS patients should be classified according to the pathogen and tested on those whose CFS was only after EBV infection, for example.

The improvement in CFS patients is logical because it decreases B cells with latent infection as in autoimmune diseases. But these patients may not fully recover after treatment, as there may be a reservoir of EBV in plasma and/or epithelial cells or difficult to access b-cells, as Prof Jonathan Edwards comments. Once the treatment is finished, the B cells will be infected again and the patient's genetic susceptibility will cause problems. Therefore, treatment with adoptive immunotherapy with CD8 lymphocytes against latent proteins could be a good treatment to try, since it would destroy those cells that express some latent protein regardless of the type of cell.

 

[Learner1]

About rituximab I think that it should first be given together with antivirals to prevent herpesvirus reactivations by immunosuppressing with that treatment.

No one seems to be doing it that way. The fear is that wth no B cells, there's nothing to fight an active infection. Some foctors are giving IVIG and Rituximab together. But Rituximab has it's risks. It has really damaged some patients permanently. Selecting who might benefit and who might be damaged is critical.

But rituximab only goes against cells that express CD20. The expression of CD20 includes from the pre-B cell stage to the B cell memory stage. In addition, CD20 is expressed in more than 90% of non-Hodgkin's lymphoma B cells, but is not detected in stem cells, pro-B or plasma cells. Thus, any targeted therapy against CD20 will not act on plasma cells.

Agreed.

In addition, to see if this treatment really works, CFS patients should be classified according to the pathogen and tested on those whose CFS was only after EBV infection

And B cell types and genetics.

So, are you saying if someone had other herpes family infections, other viral infections, or atypical pneymonias, Rituximab should not be used?

Therefore, treatment with adoptive immunotherapy with CD8 lymphocytes against latent proteins could be a good treatment to try, since it would destroy those cells that express some latent protein regardless of the type of cell.

What treatment is this?

 

[Manuel]

So, are you saying if someone had other herpes family infections, other viral infections, or atypical pneymonias, Rituximab should not be used?

No, I mean to see if a treatment really works for CFS, you have to classify the subgroups first and test it in a subgroup, for example. It is not right for us to take all CFS patients regardless of the pathogen that infected them and try all of them for treatment. I mean, we'd be skipping a step, since patients would be treated without being fully diagnosed and classified.

Most pathogens that cause CFS may behave the same way by decreasing MHC class II molecules in antigen-presenting cells and the problem may be primarily in B cells. But this must first be demonstrated one by one to verify this evasion mechanism and that they have no others. Also, as I mentioned before, you have to know what types of cells can infect each pathogen. Because if we give a treatment that only goes to one type of cell there will always be a reservoir in other types and the treatment will be useless.

Adoptive immunotherapy is a treatment used to help the immune system fight diseases such as cancer and infections with certain viruses. In-house samples of T cells (EBV-specific CD8 lymphocytes) are taken and cultured in a laboratory. This procedure increases the number of T cells capable of killing cancer cells or fighting infection. These T cells are returned to the patient to help the immune system fight these diseases.

This treatment has had good results in multiple sclerosis reducing signs and symptoms, and has been able to eliminate some cancers. In addition, it can be used in conjunction with other treatments to increase its effectiveness.

 

[Dan_USAAZ]

@Berzerkerina @Learner1
About rituximab I think that it should first be given together with antivirals to prevent herpesvirus reactivations by immunosuppressing with that treatment.

No one seems to be doing it that way.

While I do not know how rituximab has been prescribed for ME/CFS, I can add that for my father, antivirals were prescribed along with his rituximab treatment. He will be on B cell depleting medication for the rest of his life and this therapy includes antivirals. The antiviral was not to treat any observable active virus, but rather the latent viruses that we all have which will presumably not be adequately controlled under B cell depleting therapy. At least that is my understanding….

 

[Learner1]

That's a good idea. My father had a serious shingles outbreak soon after his Rituximsb treatment.

 

[heapsreal]

An effective treatment to increase nk function would go along way in treating different viral infections implicated in cfsme. Low nk function found in many cfsme should be reguarded as a functional immune deficiency and treatment should be aimed at the nk cell function. Its been looking straight at cfs research for decades but only a few have noticed it seems. Only the old drug immunovir has been used but only with minor effects, new research into this is needed.

 

[Manuel]

Hi @heapsreal
Adoptive immunotherapy can also be done with NK cells. It would be interesting to culturate one's own specific EBV CD8 cells together with NKs and reintroduce them into patients. This may further increase the effectiveness of the treatment.

 

[Learner1]

Has anyone done this in a human ME/CFS patient?

 

[Gemini]

The antibodies against EBNA I'm asking for are IgG (I forgot to put it in, sorry). Anyone who has been infected with Epstein Barr virus has these positive antibodies. But in our disease (as in multiple sclerosis) I think it's much higher than normal.

@Manuel, interestingly EBV antibody levels have been used by the Social Security Administration here in the U.S. as far back as 1999 as one of the labs they accept(among other factors) for ME/CFS disability determination.

Issued in 2014 Social Security Ruling SSR 14-1p specifies these levels as acceptable:

EBV capsid antigen greater than/equal to 1:5120, or
EBV early antigen greater than/equal to 1:640

You're an excellent writer. Have you thought about adding citations/references and submitting your article to a journal?

 

[Manuel]

Has anyone done this in a human ME/CFS patient?

I don't think they've tried it. I believe that good results would be obtained, but it must be specific according to the pathogen that has infected them.

 

[Gemini]

Another more invasive test is to perform PCR to EBV (does not have to be positive in the blood) on swollen tissue samples, such as the intestinal mucosa or muscle tissue if there is any myopathy.

@Manuel you make a very important point here.

Two decades ago there was a study (unpublished) of an ME/CFS patient who underwent an endoscopy. Tissue samples of the esophagus, stomach and small intestine were PCR tested for EBV and HHV-6. Patient's blood was also tested. Dharam Ablashi, EBV expert who discovered HHV-6 collaborated on the study.

EBV results: stomach and small intestine 'positive' for EBV; esophagus 'negative.' Blood sample 'slightly positive.'

HHV-6 results: esophagus, stomach and small intestine 'positive' for HHV-6. Blood sample 'negative.'

In general, most of the activities of the immune system happen in tissue not blood.

 

[Manuel]

Thank you very much @Gemini .
The problem with the early antigen EBV , is that many CFS patients have periods where it is positive and others where it is negative (due to reactivations). But the real cause of this disease is the cells where this virus is dormant. And one way to measure it would be by levels of antibodies to EBNA.

I was thinking about looking for some scientific journal to publish the article in. But there were several factors why I decided to publish it this way. Being such an extensive article, many scientific journals set limits and I wanted all the content to be there so that this disease could be understood, since it is multisystemic. Besides, to publish in them, I would have to translate it into English and I didn't have a good level of English to do it. To write around here and translate the article more or less, I had to use online translators. And he wanted people to have it as soon as possible so they could give it to their doctors and get them to listen to them more.

What do you mean by citations/references? You talk about the bibliography? At the end of the article you will find the bibliography and in each part of the article you will find the citations of the articles where the information has been taken.

Greetings and thank you very much for the information. I didn't know that in your country there were already antibody values against EBV as part of the official diagnosis of CFS.

 

[Manuel]

@Manuel you make a very important point here.

Two decades ago there was a study (unpublished) of an ME/CFS patient who underwent an endoscopy. Tissue samples of the esophagus, stomach and small intestine were PCR tested for EBV and HHV-6. Patient's blood was also tested. Dharam Ablashi, EBV expert who discovered HHV-6 collaborated on the study.

EBV results: stomach and small intestine 'positive' for EBV; esophagus 'negative.' Blood sample 'slightly positive.'

HHV-6 results: esophagus, stomach and small intestine 'positive' for HHV-6. Blood sample 'negative.'

In general, most of the activities of the immune system happen in tissue not blood.

Yes, you're right.
For example, in uterine cancer due to human papillomavirus infection, PCR is negative in the blood. It is only positive when the tissue sample is taken. Another example, in inflammatory bowel diseases such as Crohn's disease, ulcerative colitis... They tested positive for PCR on the Epstein Barr virus in the intestinal mucosa but not in the blood. This indicates that there are certain tissues where there is an accumulation/reactivation of this virus. And that this test could also be performed on CFS patients for diagnosis. Other methods, such as in situ hybridization with a probe that detects EBV-coded RNA (EBER), could also be used to locate latent EBV in tissue samples, or Immuno-FISH.

 

[heapsreal]

Hi @heapsreal
Adoptive immunotherapy can also be done with NK cells. It would be interesting to culturate one's own specific EBV CD8 cells together with NKs and reintroduce them into patients. This may further increase the effectiveness of the treatment.

Agree.

But id just like to see more drugs that increase nk function in general just because many infections are implicated in cfsme. Even if ebv is an issue, im guessing its probably suppressing the immune system and allowing coinfections, thats my reasoning behind some type of drug to increase nk function in a general way.

Ive seen in russia they sell ivig specific to different infections such as ebv and cmv. Unsure of how effective they would be??

 

[heapsreal]

The year i had cfsme it started with cmv. At the time i was tested for ebv and negative. A couple of months later i had mono type symptoms but held off going to the dr straight away. Blood work showed ebv but not igm only igg antibodies, i suspect i was too late getting blood work to catch igm antibodies but as the recent testing in the year showed i was negative, this ebv test was reguarded at the time as an active infection, i cant recall but probably had high lymphocyte count etc.

Several years later when i saw a cfs dr and told him my history of cmv, vzv and ebv all within several months he retested cmv and ebv, ebv came back totally negative to life long ebv igg antibodies. Apparently this loss of igg antibodies later on was common in the lake Tahoe cfs outbreak. Is some peoples immune memory to ebv lost???

Cmv and vzv have been on going issues for me since cfs onset.

 

[pcmenten]

@pcmenten
My intention was to gather everything that the epstein barr virus could do. One of the main things is the inflammation of the intestinal mucosa and how the serotoninergic system is altered. I hope this information can help people get more attention from some doctors.

I keep seeing references to the involvement of macrophages in health outcomes. Examples:

• a new avenue of pain treatment involves blocking macrophages.
• MS treatment includes Rituximab, which lowers white blood cell counts.
• EBV is an infection of white blood cells. Turns them into zombies.

What also is catching my attention is the recent interest in fasting as a health practice. Not for reasons of weight loss, although weight loss is normal, but for maintenance of the gut biology. But fasting also lowers white blood cell count. When the body thinks it is in survival mode, it starts doing some overdue 'housecleaning', including reducing excess white blood cells. Humanity used to experience short-term starvation much more frequently, and it might actually be what we evolved to tolerate and exploit. It might be an important health practice along with good sleep hygiene, healthy diet, physical activity, and socialization.

The research and understanding of the biological population of a healthy gut is incomplete, and I expect that to be the case for quite a while to come. The gut is complicated. It is a habitat with many still unknown species. In the meantime, I'm going to continue to experiment with fasting to see if that helps my symptoms.

Thanks for the research.

Paul