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Elevated EBV, HHV 6 -- what does this mean?

IreneF

Senior Member
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Normally, when the immune system is exposed to a pathogen, it creates a "memory" and responds faster the next time. It continually produces a certain level of antibodies to that pathogen. Over time, in the absence of more stimulation, the response fades - faster for some pathogens than others.

It's very different when you are talking about viruses that are persistent. Some examples would include HIV, HTLV-1/2 (also retroviruses), human herpesviruses (including VZV - chicken pox / shingles), and (sometimes) hepatitis b or c (although these may not always be chronic). Because the viruses are not eliminated entirely, the immune system continues to be stimulated, and over time, the body makes better and better antibodies against them (it selects for those that work best). Titers tend to rise over time to persistent infectious agents. People with herpes simplex tend to have very severe first outbreaks, followed by outbreaks of decreasing severity and frequency over time as the body makes more and better antibodies and learns to control the infection.

Shingles occurs only (to the best of my knowledge) in unvaccinated people who were exposed to wild type varicella virus and first developed chicken pox, and later, due to aging, the immune system starts to become less effective and the virus is able to break through. I don't think we really know how the vaccine works, although I may be wrong on this. My understanding is that there are multiple possibilities. It may be that the live, attenuated virus establishes a long term infection, which continues to offer immunity. It may be that it only primes the body to react more quickly to vzv when it encounters the wild type version, which then establishes a long term infection. It may be that no long term infection occurs - although I doubt this. It's also possible both strains coexist.

I believe the VZV strain used is not replication defective, just attenuated and less pathogenic. If it were a replication defective live virus, then it would not establish any infection.

There is currently some controversy in the development of vaccines against EBV, CMV, and the herpes simplex viruses. Some argue that even live attenuated is too dangerous, although we already use it in VZV. It does seem to produce a much more robust response than VLP glycoprotein based vaccines, and the VZV vax appears quite safe.
If a person is already less immune competant, than a vaccine with a live virus seems like a not-so-good idea.
 

IreneF

Senior Member
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San Francisco
@heapsreal - Can you show me a published study that proves that ME patients have higher titers on average against any herpes virus?

I agree with you that there are subclasses and that we are not all the same. I could even believe that there are people with more issues with herpes viruses, or particular herpes viruses, I'm just not convinced that this group is overrepresented among ME patients. i.e. I'm not sure it makes any more sense to treat ME patients with antivirals than non-ME patients.
Valcyte also has anti-inflammatory effects.
 

msf

Senior Member
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3,650
It still seems likely that he will be alive to the possibility of bacterial involvement.
 

Eeyore

Senior Member
Messages
595
If a person is already less immune competant, than a vaccine with a live virus seems like a not-so-good idea.

There are some cases where this is true, and some cases where it is not. For example, you would not give a live attenuated vaccine to someone who has undergone bone marrow ablation and has no immune system (awaiting bone marrow or stem cell transplant). In cases of mild immune deficiency, or certain types, it may not be harmful at all to use them.

There doesn't appear to be any evidence at all that ME patients do badly with live attenuated vaccines (at least not that I'm aware of). There seems to be some evidence that ME patients may have problems with some non-infectious vaccines. (Dr. Byron Hyde noted many of his patients got worse after the Hep B vax, which has no infectious potential - it doesn't even start as an infectious particle, so it has no potential to cause infection at all whatsoever, in anyone, but it does stimulate the immune system - which can cause problems).

There isn't really any good evidence that ME patients are immunosuppressed to any substantial degree. Many ME patients think they are, but this doesn't appear to be grounded in science. There does appear to be significant immune dysregulation. However, we do not observe ME patients developing opportunistic infections common in immunosuppresed patients.

In fact, the most effective ME therapy right now is probably rituximab, which is immunosuppressant. This suggests that ME is a state of immune overactivation or immune dysregulation rather than immune suppression. Immune suppression seems to have potential to improve ME symptoms.
 

Eeyore

Senior Member
Messages
595
Is not EBV classic long term manifestation fatigue?

EBV does cause mono, which can cause prolonged fatigue, but not of indefinite duration. Also, mono fatigue doesn't really look that much like ME fatigue - which is more appropriately characterized as exertional intolerance.

I think early on, it was reasonable to suspect EBV as potential cause of ME, but the science hasn't supported it. ME patients don't have more EBV, don't have higher antibody titers, and don't have more EBV by PCR. They do not have higher rates of seropositivity for EBV. There appears to be no difference between ME and non-ME patients with regard to EBV.
 

heapsreal

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@heapsreal - Can you show me a published study that proves that ME patients have higher titers on average against any herpes virus?

I agree with you that there are subclasses and that we are not all the same. I could even believe that there are people with more issues with herpes viruses, or particular herpes viruses, I'm just not convinced that this group is overrepresented among ME patients. i.e. I'm not sure it makes any more sense to treat ME patients with antivirals than non-ME patients.


You must have a different search engine to everyone else as there is plenty of studies on ebv in cfsme, especially dr lerner, dr glaser. Also evidence of different forms of ebv infections. Even recent research involving ebv as a trigger for autoimmune disorders.

Early this year i posted a study done in australia of a researcher successfully treating ms with t cells being treating with a vaccine for ebv and then t cells being infused back into the patient.

I guess its easy to be blinded by your own theories and cherry pick the studies that best suit them. Although i haven't seen u post and studies to back your opinions even though you request others to post studies, to back their opinions.

simply putting in herpes viruses cfsme antivirals into a search engine will give you more than enough research on the subject

as for there being no compromised immune function in cfsme, what is the difference between the recognised nk defiency disorder and low nk function found in cfsme. nk defiency disorder is commonly treated with antivirals to prevent herpes virus infections and is a standard treatment for this disorder.

dr garth Nicholson has done plenty of research on cfsme which shows the longer one is ill , the more infections they find. Im sure your smart enough to find his research by using google.

If cfsme does turn out to be an autoimmune disorder, that doesnt exclude people from also carrying chronic infections.
 

Eeyore

Senior Member
Messages
595
From Halcyon's link, this more or less is how I see it:

CFS onset typically goes along with a viral illness. Various viruses have been reported to trigger CFS. In 2009, it was published that the retrovirus XMRV is linked to CFS. Although this turned out to be a laboratory contamination, it called attention to this so far neglected disease [18], [19], [20], [21]. Herpes viruses as cause of CFS have been discussed for decades. However, stringent evidence for a clear association of enhanced or altered viral load and disease is still lacking [22], [23], [24], [25], [26], [27]. Further, in CFS data about altered serological responses against viruses of the herpes group are not consistent. Several groups reported more frequent detection of HHV6/7 load and elevated antibody titers [27], [28], [29], [30], [31] a finding that was not confirmed by others [32], [33]. Increased IgG to human cytomegalovirus (CMV), EBV viral capsid antigen (VCA), HHV-6, Herpes-Simplex Virus (HSV)-1, HSV-2 and Coxsackie viruses were reported in CFS in some studies [34], [35], [36], but not in others [37], [38].

I have read that article before and I do find it interesting that some patients have no EBNA antibody but high VCA antibody. That is the one study that's shown anything really odd about EBV and ME. I'm not sure what it means, or if it's significant, but yes, it's interesting and further studies to confirm it would be interesting.

Nicholson has focused most of his work on bacteria and treating ME with abx. He has some wacky ideas but also is well known for his important role in the development of the fluid mosaic model of the cell membrane. Some of his stuff is really wacky though.

I do think there is some evidence that EBV may play a role in MS - much better evidence than for ME. So far all we've seen in ME is one small study showing what may be a difference in the types of antibodies produced against EBV. It could be significant but it's no smoking gun yet.

If we could use EBV and HHV6 titers as biomarkers for ME, we'd have an ironclad diagnostic test. So far, we don't have one.

There may be NK dysfunction in ME. Personally, I think there probably is. My point was that ME is not a state of severe immunosuppression where one would see opportunistic infections. In fact, my ME doc says he sees far FEWER URI's in ME patients. They actually get sick much less - suggesting the immune system is on alert and preventing infection.

There are various kinds of functional NK deficiencies. Severe functional NK deficiency such as HLH is treated with ultra high dose corticosteroids, ciclosporine, and other immunosuppressants. It is fatal without bone marrow transplant. The cause of death is immune system overactivation or sometimes malignancy in milder cases where people survive long enough (generally hematological, usually lymphoma). Viral infections can be fatal not because the body can't fight the virus but rather because the body cannot resolve the inflammatory response normally. This is also the mechanism in MAS or SJIA. The immune system can become so dysregulated and overactive that macrophages proliferate and phagocytose RBC's in large numbers - which ends up being fatal in most cases.
 

Eeyore

Senior Member
Messages
595
So far, the most effective treatments for me have been various forms of immunosuppression. I would try rituximab if it were available at this point. I think there are other monoclonals already used in cancer and autoimmune disease that would be effective. Klimas is pretty excited about anakinra (il-1 blocker) and I'd love to see that studied.

Cytoxan (cyclophosphamide) is also being used, although I must admit I'd be a bit scared of using alkylating agents. For those that do not know, this is an old chemo drug and in high doses produces classic "movie chemo" symptoms... It works by crosslinking DNA and is a derivative of mustard gas used in WW1. So far though there is preliminary evidence that it works in ME patients who do not respond to rituximab. It's used to treat a lot of autoimmune diseases as well.
 
Messages
15,786
There doesn't appear to be any evidence at all that ME patients do badly with live attenuated vaccines (at least not that I'm aware of). There seems to be some evidence that ME patients may have problems with some non-infectious vaccines.
There's been two or three studies of flu vaccines in ME patients. Basically they work, but they also trigger an abnormal immune reaction of unknown duration, lasting at least 30 days. My impression of the relevant papers was that they do not know exactly what is happening, nor why, nor what the ultimate effects of the reaction are.

Pre-existing immunosupression wouldn't be the only reason to have an adverse reaction to vaccines. Hence I'd probably stay away from vaccines as much as is reasonable while I have ME, with the additional assumption that live vaccines would provoke the same mysterious effects in us as the flu vaccines.
 
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15,786
Also, mono fatigue doesn't really look that much like ME fatigue - which is more appropriately characterized as exertional intolerance.
I would disagree. Back in the good ol' days, it was one of those childhood/teenage infections which was known to sometimes result in prolonged illness which often required bed rest. And the description of my cousin's temporary teenage experience of mono sounds eerily similar to what I've been experiencing with ME.
 

IreneF

Senior Member
Messages
1,552
Location
San Francisco
I would disagree. Back in the good ol' days, it was one of those childhood/teenage infections which was known to sometimes result in prolonged illness which often required bed rest. And the description of my cousin's temporary teenage experience of mono sounds eerily similar to what I've been experiencing with ME.
I had mono when I was 16. It felt very much like certain aspects of CFS.
I would disagree. Back in the good ol' days, it was one of those childhood/teenage infections which was known to sometimes result in prolonged illness which often required bed rest. And the description of my cousin's temporary teenage experience of mono sounds eerily similar to what I've been experiencing with ME.
 

IreneF

Senior Member
Messages
1,552
Location
San Francisco
So far, the most effective treatments for me have been various forms of immunosuppression. I would try rituximab if it were available at this point. I think there are other monoclonals already used in cancer and autoimmune disease that would be effective. Klimas is pretty excited about anakinra (il-1 blocker) and I'd love to see that studied.

Cytoxan (cyclophosphamide) is also being used, although I must admit I'd be a bit scared of using alkylating agents. For those that do not know, this is an old chemo drug and in high doses produces classic "movie chemo" symptoms... It works by crosslinking DNA and is a derivative of mustard gas used in WW1. So far though there is preliminary evidence that it works in ME patients who do not respond to rituximab. It's used to treat a lot of autoimmune diseases as well.
Rituximab is (or was) available thru Dr. Kogelnik in Mtn. View, CA. Sadly, it did not work for me.
 

heapsreal

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So far, the most effective treatments for me have been various forms of immunosuppression. I would try rituximab if it were available at this point. I think there are other monoclonals already used in cancer and autoimmune disease that would be effective. Klimas is pretty excited about anakinra (il-1 blocker) and I'd love to see that studied.

Cytoxan (cyclophosphamide) is also being used, although I must admit I'd be a bit scared of using alkylating agents. For those that do not know, this is an old chemo drug and in high doses produces classic "movie chemo" symptoms... It works by crosslinking DNA and is a derivative of mustard gas used in WW1. So far though there is preliminary evidence that it works in ME patients who do not respond to rituximab. It's used to treat a lot of autoimmune diseases as well.


Anakinra looks interesting as elevated IL 1 cyokine seems to implicated in sleep problems or the sleep problems cause the increased IL 1 or both.

I think it was info on xyrem where i read that improving sleep quality with xyrem decreased IL 1.

IL 1 antagonist seem popular in autoinflammatory diseases . Cfsme probably has more similar characteristics with autoinflammatory than autoimmune diseases .
 

heapsreal

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XMEN disease, a rare immune deficiency caused by a defective magnesium transporter gene, is also characterized by high EBV titers. These are a downstream effect of the underlying defect, and not the cause. Another reason why I am no longer very interested in my blood work.

https://en.m.wikipedia.org/wiki/XMEN_disease


Lack of interest in blood work for me is because i/we start to realize that there is so much they dont really know and cant tell with blood work .
 

sarah darwins

Senior Member
Messages
2,508
Location
Cornwall, UK
Would the work published by Hornig et al earlier this year be relevant here?

“It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop.” - Hornig

Most studies don’t distinguish between short and long-term patients. If testing for pathogen activation is based on immune response, it’s presumably going to be a very different story for the two subgroups. Wouldn’t this make attempts to generalise about immune activity and the pathogenic activity it indicates very problematic?

Perhaps this explains why long-term me/cfs sufferers with only moderate test signatures for viral activation may find antivirals helpful? If their immune systems are in a state of burn-out, the antiviral may be doing what the autoimmune system can’t. Subsequent testing might show little change in cytokine activation, even if the patient is feeling a lot better. ???

Sidenote: as well as routine PEM episodes, I sometimes get longer, slow motion crashes. I’ve just been through one lasting about three weeks. These invariably involve swollen glands. Viral?

ps. pls don’t shout at me if the above is nonsense! I’ve been following this quite demanding thread because it’s very instructive. My remarks are more an attempt to get to grips with this than assertions.