Dr Martin Lerner's abortive infection theory of ME/CFS

[Hip]

In any case, I always wondered if there's anything to substantiate Lerner's proposed mechanism here. I understand how the immune system could be preventing the virus from completing its infectious cycle, while viral proteins are still synthesized by the cells' ribosomes or whatever. However, is this documented anywhere with EBV, or with any herpesvirus for that matter?

I am going to answer your above quoted question in this thread, which is a more appropriate place.

There is not much evidence to substantiate Martin Lerner's theory of abortive herpesvirus infections in ME/CFS (but there is good evidence to substantiate a very similar phenomenon called non-cytolytic infection in the case of enterovirus-associated ME/CFS).

It's not the immune system as such which prevents the virus from completing its replication cycle; rather abortive infection is due to the virus entering the wrong sort of human cells — cells which do not possess the right internal conditions to facilitate full viral replication (these wrong sort of cells are called non-permissive cells).

Abortive infection has been observed in cell line experiments in vitro: if you use a cell line of cells that are non-permissive for EBV, you can observe an abortive infection. I am not sure if herpesvirus abortive infections have been observed in vivo. Certainly though HIV abortive infections are known to occur in vivo.

 

[JeanneD]

That leads me to another unsolved question about Dr Lerner's theory: Where does the initial worsening/herxheimer reaction come from when you start Valacyclovir? It doesn't kill the virus, just stops it from replicating, so technically it can't be a real Herx/die off reaction. Could it be possible that Valacyclovir induces apoptosis in (some?) infected non-permissive cells and that causes the initial worsening?

Take this with a grain of salt as it was a long time ago, so I might have got it mixed up with something else in the ensuing years, or I might have not understood correctly.

IIRC, Dr Lerner got miffed when people called the early rough rxns to Valcyte herxing. It is definitely not herxing. That doesn't happen with viral infections. He speculated that in many of his patients, their immune system has been reacting unsuccessfully to the abortive infections for so long that their immune systems (to put it in layman's terms, not medical terms) got worn out or gave up trying to fight it. Once the Valcyte slowed the abortive infection, the immune system recognized it could now fight back and came back online with a vengence, maybe over-reacting. Valcyte rxns in ME patients look like strong immune rxns -- like a very bad flu. That certainly fit my experience.

My daughter had no side effects from Valcyte while I had a pretty bad one (worth it though, given how much I improved). The speculation is that my daughter's younger immune system and less severe illness for less time kept her immune system from "giving up" while my older, more challenged immune system was exhausted and so when it got help from Valcyte, the response was much greater.

As long as we saw Dr Lerner, he did no immune testing, so he never tested this idea to my knowledge. It was just a speculation on his part.

Later, when we switched specialists and got immune testing, my immune system was more out-of-whack than my daughter's, although we both had abnormalities.

 

[imitate-past-reign]

Note that only one a million B-cells is infected with EBV at all, while native T-cell dysregulation (the genetic / environmental component) causes less clearance within the CNS compartment of EBV and proliferation of even uninfected B-cells. This is why Rituximab is not the greatest monotherapy. Clearance of EBV by Rituximab is almost always in concert with CHOP chemotherapy.

Moreover, Rituximab is always taken with high-potency glucocorticoids which further dysregulate this system.

It is not unreasonable to suggest that 1% of the population will have permanent sequelae from EBV/CMV infectious mononucleosis, and that would present as obvious Chronic Fatigue syndrome, regardless of the semantic arguments about the lytic cycle.

The EBV / CMV connection is fine, but why are the treatments is a derivative of acyclovir from the early 1980s?

- Autologous Natural Killer Cell adoptive immunotherapy
- Autologous T-Cells against EBV
- CMV- and EBV-specific immunoglobulins

Why is the leading theory for CFS a shoehorned autism trial that was poorly blinded, using an IV-drug with a terrible therapeutic index requiring repeated dosing, using a biochem 101 theory about energy production?

Especially when none of the above have been tried.

 

[rodgergrummidge]

The EBV / CMV connection is fine, but why are the treatments is a derivative of acyclovir from the early 1980s?

- Autologous Natural Killer Cell adoptive immunotherapy
- Autologous T-Cells against EBV
- CMV- and EBV-specific immunoglobulins

Why is the leading theory for CFS a shoehorned autism trial that was poorly blinded, using an IV-drug with a terrible therapeutic index requiring repeated dosing, using a biochem 101 theory about energy production?

Especially when none of the above have been tried.

welcome to PR @imitate-past-reign

Perhaps there was a typo in your above comment? Are you suggesting that Autologous Natural Killer Cell adoptive immunotherapy, Autologous T-Cells against EBV, CMV- and EBV-specific immunoglobulins would be better treatments for EBV-induced CFS than antivirals? Or the other way around? Which IV-drug were you making a comparison to? Ritux?

Rodger

 

[imitate-past-reign]

Thanks for your welcome to the forum. I’m on my phone so this isn’t as lucid as normal. Sorry for the mix-up - yes, I’m glad Valcyte works for some but it is crude (both adverse and efficacy) and expensive.

Roger, I was referring to suramin. The leading candidates for treatment in CFS are cyclophosphamide and suramin I suppose. That’s pretty dire in terms of innovation.

Cyclophosphamide diminishes the t and B cell response which goes against the framework here. I am really underselling how terrible an idea that is, but it might actually improve immune antibody type patients (women over 30 post-natal).

In klimas et al. 2001 they removed the patients lymph nodes under anesthesia, expanded, replaced them under anesthesia. Trial was moderately successful - trial sponsor pursued other applications.

They didn’t need to undergo surgery, you just draw blood, expand the t-cells, re-injection.

The question I would have to be to those who control private funding for immunotherapeutic treatment like this is - “Do you have a better idea?” And if they do, it’s great for all of us.

 

[heapsreal]

Bump.

 

[Blazer95]

Maybe if we favor CD4 differenciation into Th17, it would allow them to survive and to restore equilibrum between Tregs and Th17?

Further mechanistic studies demonstrated that the combination of CIM and LMS promoted DC activation and blocked anti-inflammatory cytokine IL-10 and TGF-β production in CD4(+) CD25(+) T cells. These findings suggest that CIM and LMS have the synergistic and additive ability to enhance cellular response to HBV DNA vaccine, which may be mediated by DC activation and inhibition of anti-inflammatory cytokine expression. Thus, the combination of cimetidine and levamisole may be useful as an effective adjuvant in DNA vaccinations for chronic hepatitis B virus infection.
Synergistic and Additive Effects of Cimetidine and Levamisole on Cellular Immune Responses to HBV DNA Vaccine in Mice.. Available from: https://www.researchgate.net/public...r_Immune_Responses_to_HBV_DNA_Vaccine_in_Mice [accessed Nov 11 2017].

In a case report:

HIES patients have impaired differentiation of Th17 T cells from mutations in STAT3.5 Experimental models in which Th17 cells or Th17 cell‐dependent cytokines are defective have shown that immunity to several extracellular bacteria, including Staphylococcus aureus, Klebsiella pneumoniae and Candida albicans, is impaired.6
....
Other therapies. Isotretinoin, cyclosporin A, and plasmapheresis have been tested on a few patients but are not generally indicated.[URL='http://www.sciencedirect.com/science/article/pii/S0873215914000038#bib0020']4,11 H2 antagonists like cimetidine seem to improve symptoms.[/URL]

(I found only anecdotal reports that cimetidine may improve the differenciation of Th17 at the expense of Tregs)

I found also a paper about synergia between Praziquantel and Cimetidine... Was Praziquantel tryed by some patient here?

it may be an old post, but has anyone found some useful th17 inducers?
i am in urge to increase my severly difficent th17 response

so far i have found anecodical evidence that echinacea and reishi may be able to partially increase th17 but there has been conflicting information, especially around the mushrooms.

thanks in advance dear friends.