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

[pattismith]

Dr Lerner's abortive infection hypothesis of ME/CFS did not get the attention it deserves, because it seems to me that this theory could explain several observations about ME/CFS, and in addition, this theory could neatly tie together herpesvirus-associated ME/CFS with enterovirus-associated ME/CFS into a single framework of understanding (because as we shall see in a moment, the non-cytolytic enterovirus infections found in ME/CFS patients can be considered as a sort of abortive infection).
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Days ago you showed me a picture of enterocytes from an enterovirus infected gut, with a big load of enterovirus in it. It is consistent with an "abortive infection"? I would expect a smaller cell load of virus in an abortive infection, wouldn't it?

Here a study about HBV, would you tell me if asymptomatic carriers are consistent with an "abortive infection":

Expression of CD39 on FoxP3+ T regulatory cells correlates with progression of HBV infection

Abstract
Background
Although it is known that regulatory T cells (Tregs) can suppress the function of effector T cells, and may contribute to impaired immune response, the precise role of Tregs during the course of hepatitis B virus (HBV) infection remains to be elucidated. A newly identified subset of the CD4+Foxp3+ Tregs, the CD39+ Tregs, has been associated with viral infections and autoimmune diseases. Therefore, we hypothesized that this discrete Treg subset may contribute to the chronic infection of HBV.

Results
Initial characterization studies of healthy peripheral CD39+FoxP3+CD4+ T cells revealed that the majority were CD45RA- Treg cells. Subsequent analysis of HBV-infected patients (38 asymptomatic HBV carriers (AsCs), 37 chronic active hepatitis B (CAH), 29 HBV-associated acute-on-chronic liver failure (ACLF)) and healthy individuals (25 controls) was conducted to assess association with HBV copy number and the liver injury marker alanine aminotransferase (ALT).
A higher percentage of CD39+ Tregs was detected within the population of FoxP3+CD4+ T cells in peripheral blood of Asymptomatic carriers patients.
Moreover, the percentage of CD39+ Tregs was significantly less in Chronic Active Hepatitis and Acute on chronic liver failure patients.
The increased proportions of circulating CD39+ Tregs were positively correlated with serum viral load, but inversely correlated with serum ALT level.

Conclusion
These findings not only suggest that CD39+ Treg cells may be involved in HBV disease progression but also identify CD39+ Tregs as a dynamic immune regulatory cell population that may represent a new target of immunomodulatory therapeutic interventions.

 

[Wonkmonk]

In response to your questioning Dr. Lerner's theory that herpes viruses can occur in the heart, I can offer my experience.

Dr Lerner found inverted T-waves, tachycardia and other heart abnormalities in his patients. He checked them with Holter monitor and in some patients also with heart biopsies. He stopped doing biopsies after complications because the heart tissue seems to be strongly affected in some patients which increased the risk of bleeding etc.

 

[Hip]

Here a study about HBV, would you tell me if asymptomatic carriers are consistent with an "abortive infection":

I am not seeing any connection between the CD39 T-reg paper you quoted and abortive infections. Do you have some particular thoughts about why these might be connected?

Days ago you showed me a picture of enterocytes from an enterovirus infected gut, with a big load of enterovirus in it. It is consistent with an "abortive infection"? I would expect a smaller cell load of virus in an abortive infection, wouldn't it?

The non-cytolytic enterovirus infections found in ME/CFS patients I think can be considered as similar to an abortive infection. There are differences between abortive infections and non-cytolytic infections, but I they are similar in some respects.

The first post of this thread has a section (called "Unifying the Herpesvirus and Enterovirus Etiology of ME/CFS") which examines the similarities that abortive infections and non-cytolytic infections have, as well as their differences.

 

[Hip]

(b) those patients whose CFS is caused by EBV non-permissive infection (and only EBV, not other viruses). In those patients, Rituximab kills EBV's main reservoir (memory B-cells). That is a big step towards ending the non-permissive infection as detailed by @Hip above, and that's why some of them make a very pronounced recovery after 3-6 months (which coincidentally is exactly the timeframe Dr Lerner says antivirals need to start working). But in most cases, they don't kill all the B-cells and EBV lytic replication may continue in some permissive cells or semi-permissive cells elsewhere in the body, so new memory B-cells are reinfected and non-permissive replication starts all over again after some time, if Rituximab is discontinued. But in a lucky few, repeated Rituximab treatment clears EBV entirely (I think there is a study in which Rituximab did that in some patients) or puts the body into a position to fight it back into latency, i.e. a few patients are cured. --> So most of the patients in this group also fall in buckets (2) and (3) and some lucky few fall in bucket (1).

I think that's a good analysis of how rituximab might work in the case of the abortive EBV infection theory of ME/CFS.

To support your analysis, it's interesting to note that chronic active Epstein-Barr virus infection of B-cells (which can make people very sick) is different to the disease of ME/CFS. In Lerner's theory, the ME/CFS is a chronic abortive EBV infection of non-permissive cells.

Fluge and Mella actually successfully treated one very sick patient with chronic Epstein-Barr virus infection (not ME/CFS) using rituximab to kill the EBV-infected B cells, and this rituximab treatment completely cured her within 3 days of the infusion (see this post for further details).

This shows that ME/CFS cannot be due to a chronic active EBV B-cell infection (if it were, ME/CFS patients would also be cured in a matter of days after rituximab infusion).

Rather, the issue in ME/CFS, according to Dr Lerner, is a chronic abortive infection in non-permissive cells.

Dr Lerner posits that abortive EBV infections in the body may be supported and replenished by viral particles from productive EBV infections located elsewhere in the body (such as productive EBV infection in the B-cells).

So when you reduce or eliminate these EBV productive infections in the body (with antivirals or rituximab), you don't get any immediate improvements in ME/CFS symptoms (because these productive infections were not the cause of ME/CFS); but because the abortive infections are no longer being replenished by viral particles from the productive infections, so over some months these abortive infections slowly dwindle, and it is only then that ME/CFS symptoms start to improve.

 

[Hip]

How does your theory fit with Dr. Davis's finding that the problem seems to be a large particle in the blood?

As far as I know, Dr Martin Lerner did not mention anything about how his abortive infection theory of ME/CFS could give rise to the energy metabolism dysfunctions that several studies have found in ME/CFS patients' cells, or the findings that there is something in the blood serum that is causing these dysfunctions.

So we can only try to extrapolate Dr Lerner's ideas ourselves. In an attempt to do this, if you look at this thread, which is about how chronic non-cytolytic enterovirus infections can give rise to an ANT autoantibody that targets and disables the mitochondria, that shows how such chronic enterovirus infections can induce an autoimmune attack on mitochondria.

Such enterovirus-induced anti-mitochondrial autoantibodies could well be the large particle in the blood you are referring to.

So that explains how, in the enterovirus subset of ME/CFS, a chronic non-cytolytic infection may give rise to autoantibodies in the serum which disable mitochondria. And possibly something like this may also occur in Dr Lerner's herpesvirus abortive infections, presumed to exist in the herpesvirus subset of ME/CFS.

As mentioned earlier in this thread, enterovirus non-cytolytic infections are closely analogous to herpesvirus abortive infections.

 

[pattismith]

I am not seeing any connection between the paper CD39 T-reg paper you quoted and abortive infections. Do you have some particular thoughts about why these might be are connected?

The non-cytolytic enterovirus infections found in ME/CFS patients I think can be considered as very similar to an abortive infection. There are subtle differences between abortive infections and non-cytolytic infections, but I think they are broadly similar.

The first post of this thread has a section (called "Unifying the Herpesvirus and Enterovirus Etiology of ME/CFS") which examines the similarities that abortive infections and non-cytolytic infections have, as well as their differences.

What Lerner says is:

"The cellular sites for latency for HCMV are the mononuclear phagocyte and its progenitor cells [18]. When the monocyte differentiates into the macrophage or histiocyte, infections HCMV virus production ensues, with an associated irreversible destruction of the infected cell."


So it doesn't seem very different than Hepatic virus, because they cause persistent non cytolytic infection in mononuclear/macrophage as well and can produce reactivated infections as well (in the liver).

If you have protective antibodies against one hepatic virus, you will not be allowed as a blood donor (because of your possibly infected monocytes), but your plasma will be welcome (because it carries no virus, but welcome protective antibodies)

 

[Wonkmonk]

So when you reduce or eliminate these EBV productive infections in the body (with antivirals or rituximab), you don't get any immediate improvements in ME/CFS symptoms (because these productive were not the cause of ME/CFS); but because the abortive infections are no longer being replenished by viral particles from the productive infections, over some months these abortive infections slowly dwindle, and it is only then that ME/CFS symptoms start to improve.

...but once the body starts producing new B-cells again, these B-cells get reinfected by (a) EBV reactivation of infected "old" B-cells that survived the Rituximab and/or (b) permissive or semi-permissive replication in cells elsewhere in the body, e.g. the heart (which are unaffected by Rituximab) and/or (c) any EBV virions that still circulated in the blood or were dormant in a reservoir other than the B-cells.

Once enough B-cells are infected and after some time the non-permissive infection increases again, the patient relapses and goes back to the point before s/he started Rituximab.

I recall that a CMV-negative kidney transplant recipient who receives a transplant from a CMV-positive donor has to take high-dose Valacyclovir for at least 3 months to avoid seroconversion. And this link here says the incubation period for CMV is 3-12 weeks. https://www.health.ny.gov/diseases/communicable/cytomegalovirus/fact_sheet.htm

"illness usually occurs 3–8 weeks after blood transfusion and between 4 weeks and 4 months after organ transplantation." https://www2.health.vic.gov.au/publ...s/disease-information-advice/cytomegalo-virus

Of course this is another herpes virus, but it shows how this virus family can even after long periods of time still start replicating and infecting the body. It takes a while until symptoms occur. That's consistent with small numbers of permissive or semi-permissive infected cells remain after Rituximab which then start reinfecting the body over the next couple of weeks and months.

 

[pattismith]

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To support your analysis, it's interesting to note that chronic active Epstein-Barr virus infection of B-cells (which can make people very sick) is different to the disease of ME/CFS. In Lerner's theory, the latter is a chronic abortive EBV infection of non-permissive cells.

Fluge and Mella actually successfully treated one very sick patient with chronic Epstein-Barr virus infection (not ME/CFS) using rituximab to kill the EBV-infected B cells, and this rituximab treatment completely cured her within 3 days of the infusion (see this post for further details).

This shows that ME/CFS cannot be due to a chronic active EBV B-cell infection (if it were, ME/CFS patients would also be cured in a matter of days after rituximab infusion).

Rather, the issue in ME/CFS, according to Dr Lerner, is a chronic abortive infection in non-permissive cells.

Dr Lerner posits that abortive EBV infections in the body may be supported and replenished by viral particles from productive EBV infections located elsewhere in the body (such as productive EBV infection in the B-cells).

So when you reduce or eliminate these EBV productive infections in the body (with antivirals or rituximab), you don't get any immediate improvements in ME/CFS symptoms (because these productive infections were not the cause of ME/CFS); but because the abortive infections are no longer being replenished by viral particles from the productive infections, so over some months these abortive infections slowly dwindle, and it is only then that ME/CFS symptoms start to improve.

I read the paper you quoted, thank you for the link

In his Proposal number one, Lerner said

"Alternatively, a reactivation infection with prior latent EBV or prior HCMV, or both of these herpesviruses simultaneously, may be the etiology of the CFS."
" The latent, persistent infection and recrudescent infection characteristic of the herpesviruses, EBV and HCMV, is consistent with the chronic recrudescent illness of the CFS [21]. "

In the two other proposals, non-permissive cells are hypothesized, but nothing is well explained, and nowhere Lerner use the word "abortive".

In HIV, abortive infected CD4 drive it to cell death, whereas in EBV/HCMV it doesn't seem to be the case... Is there any evidence of increased cardiomyocyte or myocyte death during this kind of infection?:thumbdown:

 

[Hip]

In the two other proposals, non-permissive cells are hypothesized, but nothing is well explained, and nowhere Lerner use the word "abortive".

In that article you mention (which is quite old, dates back to 1997), Dr Lerner proposes that ME/CFS is caused by "nonpermissive, persistent herpesvirus (EBV or HCMV) infection of the heart".

By the term "nonpermissive infection", I believe Dr Lerner is referring to an abortive infection, but he is not quite using the terminology correctly, because the term "non-permissive" refers to cells, not to infections.

For a given virus, certain cell types in the body will be permissive for that virus, meaning the virus can enter those cells and then mount a productive infection of the cell (productive means an infection which produces new virions). But other cell types in the body will be non-permissive for that virus, which either means the virus cannot enter the cell at all, or means that the virus can enter the cell, but once inside cannot produce any new virions; this latter case is an abortive infection, when the virus enters a cell but cannot produce any new virions.

So the terms permissive and non-permissive apply to cells. And the terms productive and abortive apply to infections, depending whether the virus has entered a permissive or non-permissive cell respectively.

The term non-productive infection is synonymous with abortive infection.

Note that a cell type which is permissive for one virus may be non-permissive for the next virus. So there is not any absolute condition of a cell type being permissive or non-permissive; it depends on the virus.



If you look at this 2011 paper or this 2012 paper by Dr Lerner, here he uses the terminology more correctly, referring to an abortive lytic infection.

The term lytic incidentally means that the cell is destroyed as a result of the infection.

 

[pattismith]

In that article you mention (which is quite old, dates back to 1997), Dr Lerner proposes that ME/CFS is caused by "nonpermissive, persistent herpesvirus (EBV or HCMV) infection of the heart".

By the term "nonpermissive infection", I believe Dr Lerner is referring to an abortive infection, but he is not quite using the terminology correctly, because the term "non-permissive" refers to cells, not to infections.

For a given virus, certain cell types in the body will be permissive for that virus, meaning the virus can enter those cells and then mount a productive infection of the cell (productive means an infection which produces new virions). But other cell types in the body will be non-permissive for that virus, which either means the virus cannot enter the cell at all, or means that the virus can enter the cell, but once inside cannot produce any new virions this latter case is an abortive infection, when the virus enters a cell but cannot produce any new virions.

So the terms permissive and non-permissive apply to cells. And the terms productive and abortive apply to infections, depending whether the virus has entered a permissive or non-permissive cell respectively.

The term non-productive infection is synonymous with abortive infection.

Note that a cell type which is permissive for one virus may be non-permissive for the next virus. So there is not any absolute condition of a cell type being permissive or non-permissive; it depends on the virus.



If you look at this 2011 paper or this 2012 paper by Dr Lerner, here he uses the terminology more correctly, referring to an abortive lytic infection.

The term lytic incidentally means that the cell is destroyed as a result of the infection.

Yes, I understand concepts, hopefully you did explain it very well in your first post.

But I find it confusing when the words are not used acurately.

So my question would be: do we have evidences that these abortive cytolytic infections really exist in cardiomyocytes or in myocytes with HCMV or EBV?

Edit: again in the paper you mentioned, Lerner says

"The presence of these serum antibodies to EBV dUTPase and EBV DNA polymerase indicated EBV abortive lytic replication in these 6 CFS patients"

But abortive infections only occurs when the virus is not able to replicate in the host cell, so I can't understand why he can talk about "lytic replication"...OK I understood by reading further, but he should rather talk about "aborted replication"...Just my humble opinion...

 

[Wonkmonk]

"Alternatively, a reactivation infection with prior latent EBV or prior HCMV, or both of these herpesviruses simultaneously, may be the etiology of the CFS."

I am wondering if it makes a difference in terms of how fast people become ill if it starts with a reactivation vs. first infection with EBV/HCMV. In my case, I can tell very specifically when the disease started, but it developed very slowly over several years. It started so mildly that for years I didn't even think that I could be sick. In other cases, things get very bad in a matter of weeks or even days. Maybe it was a reactivation in my case and a first infection in the others, because in the first reaction, you usually have much greater overall viral activity in the body.

For a given virus, certain cell types in the body will be permissive for that virus, meaning the virus can enter those cells and then mount a productive infection of the cell (productive means an infection which produces new virions). But other cell types in the body will be non-permissive for that virus, which either means the virus cannot enter the cell at all, or means that the virus can enter the cell, but once inside cannot produce any new virions; this latter case is an abortive infection, when the virus enters a cell but cannot produce any new virions.

As I understand it, Dr Lerner says that (a) the virus may enter non-permissive cells and cause disfunction in those cells and (b) the virus produces non-complete virions in non-permissive or semi-permissive cells which are unable to replicate to complete viruses, but still can enter and infect cells and cause dysfunction inside the cells. The immune system doesn't efficiently destroy those cells because they are not infected by "real" viruses, but over time the cell itself "realizes" it is being infected and does not function properly and then triggers apoptosis. Over time more and more cells get infected by virus or non-complete viral particles and cellular dysfunction spreads throughout the body.

At least this is my personal understanding of the articles.

 

[Hip]

So my question would be: do we have evidences that these abortive cytolytic infections really exist in cardiomyocytes or in myocytes with HCMV or EBV?

I am not sure what the evidence is. I did briefly look at some of Dr Lerner's papers on ME/CFS, but could not see much in terms of evidence. But I am a poor reader, because I suffer from significant ADHD symptoms, and find large volumes of material very hard to get through. A list of Dr Lerner's ME/CFS-related papers is found on his website here. A complete list of his published papers is found here.

Dr Lerner says that (a) the virus may enter non-permissive cells and cause disfunction in those cells and (b) the virus produces non-complete virions in non-permissive or semi-permissive cells which are unable to replicate to complete viruses, but still can enter and infect cells and cause dysfunction inside the cells.

Yes, in the case of abortive infections, the virus is not able to make all the proteins necessary to construct a full virion, but the virus does manufacture some of its viral proteins within the cell it infects, and this may cause dysfunction in the cell.

 

[jstefl]

@Hip

If your theory is correct this would seem to be very bad news for us all.

Developing a medicine that would stop a virus that isn't able to reproduce itself sounds like a very long term project. I guess that the good news is that at least we would know what we are trying to accomplish with a medication, which is more than we know now.

if Dr. Lerner got this right so many years ago, it also means that we have lost many years in the search for a treatment. The XMRV theory was encouraging because finding a treatment seemed to be possible. The abortive infection theory may involve many different viruses, making a cure even more difficult. Is it Just EBV or HHV-6, CMV, enteroviruses, or a combination of many viruses that is doing the damage?

I guess that the good news is that if this theory could be proven it would allow researchers to focus on one area instead of spreading research dollars over many disciplines.

I am hoping for an easier answer.

 

[Hip]

Is it Just EBV or HHV-6, CMV, enteroviruses, or a combination of many viruses that is doing the damage?

Dr Lerner focused on EBV, HHV-6 and cytomegalovirus abortive infections, and would treat these with Valtrex, Valcyte and Valcyte respectively. His patients would often have high antibody titers to more than one of these herpesviruses. Some of his patients would also have further co-infections with Borrelia, Babesia, Ehrlichia, Anaplasma and Mycoplasma, which would also need treatment.

I am not sure if Dr Lerner ever tested for and treated enterovirus, but that always seems to be the big divide among ME/CFS doctors: many of these doctors are either enterovirus focused like Dr John Chia, Dr Byron Hyde and the late Dr John Richardson, or they are herpesvirus focused like the late Dr Martin Lerner, Dr Daniel Peterson and Prof Jose Montoya.

The abortive infection theory may involve many different viruses, making a cure even more difficult.

Well, we know several viruses are linked to ME/CFS anyway, so there's nothing new about the idea that multiple pathogens may cause ME/CFS.

But if abortive infections are the cause of ME/CFS, then we would need to start developing antiviral drugs that can target these abortive infections. As Dr Lerner points out, current herpesvirus antivirals only target productive infections but not abortive infections.

 

[Jesse2233]

What would a drug targeting abortive infections look like in terms of its mechanism of action? Is there anything comproable on the market?

 

[Hip]

What would a drug targeting abortive infections look like in terms of its mechanism of action? Is there anything comproable on the market?

If you look at the various mechanisms by which antivirals work, you have:

Mechanism of Action of Antiviral Drugs:
(1) Inactivate extracellular virus particles (destroy the virion before it even enters the cell)
(2) Prevent viral attachment and/or entry (stop the virion from attaching to the cell, and/or entering the cell)
(3) Prevent replication of the viral genome (stop the virus from replicating its genes, needed to make new virions)
(4) Prevent synthesis of specific viral proteins (stop the virus from transcribing its genes into viral proteins).
(5) Prevent assembly or release of new virions (stop the viral proteins from assembling into new virions).

In the case of the posited abortive infections of ME/CFS, the virus has already entered the non-permissive cells, so antiviral methods (1) and (2) are of little use.

Antiviral method (3) I don't think is going to help much either, because we know that in a non-permissive cell, no new virions are made anyway.

Antiviral method (5) will not help against abortive infections, since no virions are made in these infections.

The only antiviral approach that may help is method (4), which is to inhibit the synthesis of specific viral proteins, because we know that in abortive infections, the virus is transcribing a few of its genes into viral proteins — viral proteins which may disrupt the cell.

However, even in method (4), there may not be any existing antivirals that work for abortive infections, because you would need an antiviral that inhibits the specific viral proteins being made in an abortive infection.

 

[Hip]

I was thinking that an immunomodulatory approach to herpesvirus abortive infections, where you stimulate the immune system to fight the infections, might yield results. That after all is the approach that Dr Chia uses for enterovirus infections, using oxymatrine. Though I am not sure what sort of immunomodulator would work for herpesvirus abortive infections.

 

[Wonkmonk]

If your theory is correct this would seem to be very bad news for us all.

Wouldn't it actually be good news, because if it's true we can treat it with available antivirals (at least herpesvirus). It just needs high doses and a long time to work.

 

[Gingergrrl]

@Wonkmonk Thanks for tagging me into this thread and I was curious, did Dr. Lerner ever share his thoughts about Rituximab before he passed away? Sorry if you said it and I missed it and was only able to skim this thread. I want to address a few of the points you made from my personal experience (which may or may not apply to anyone else).

Perhaps I might add - I think it hasn't come up so far - that there is a group of patients that don't get any common infections since having CFS. I am one of those, I haven't been sick even once since almost four years, which is actually impossible.

I have not had a cold, flu, or common infection of any kind since Jan 2013 which is approaching five years. Prior to this, I used to get tonsillitis or other throat infections all the time. And I have been exposed endless times when my family was sick but did not catch it from them.

My hypothesis is that Rituximab helps: (a) those patients whose CFS is caused by an autoimmunity problem not directly linked to EBV infection (e.g. possibly patients like @Gingergrrl).

My case it a bit weird b/c EBV from severe mono (in 2012) WAS one of the major triggers that occurred approx ten months before the final infection that started this illness (in Jan 2013). Two weeks later I developed POTS and never recovered. But we did not discover the autoimmunity until early 2016. I remained IgM+ and EA+ to EBV for several years but then (we suspect) it flipped into autoimmunity. I am still unclear if ME/CFS was ever my correct diagnosis. "CFS" diagnosis was given to me by several doctors, and I match it on several points, but I do not get PEM which I know is the core symptom. But I do fit into both the EBV and the autoimmune group.

In these cases, Rituximab helps in the same way as it helps Rheumatoid Arthritis patients, by killing the B-cells and reducing the autoimmune process --> Depending on how well the patient responds, they fall in bucket (2) or (3), i.e. they experience temporary partial or near-complete remission as long as they take Rituximab and usually relapse if they stop treatment.

I am a responder to Rituximab so far, and I believe it is the exact mechanism that you describe above, but since I will be doing maintenance infusions every 3-4 months for the next year, I have no idea what will happen when I stop. I have also concurrently done IVIG and no way to remove this factor.

(b) those patients whose CFS is caused by EBV non-permissive infection (and only EBV, not other viruses). In those patients, Rituximab kills EBV's main reservoir (memory B-cells).

I tested positive (at different times) for EBV, VZV, HSV, and two enteroviruses from ARUP labs (but the EV titers were below 1:320 which Dr. Chia considers active infection).

They fall in bucket (4) and don't benefit or even get much worse, because of either Rituximab side effects or because Rituximab kills their B-cells which they need to fight off another virus which causes their CFS but is not affected by killing B cells

In case this is useful, I have had no side effects from three doses of Rituximab and (so far), have not gotten any infections whatsoever. I find IVIG much harder to tolerate (from a side effect perspective) than Rituximab.

Those who benefit from antiviral therapy directed at EBV (Valtrex, Famvir) might also benefit from Rituximab

I did not benefit from anti-virals (Famvir or Valcyte) but have benefitted from Rituximab. I took Famvir 1500 mg per day for approx eight months which was a decent trial. I was not able to tolerate Valcyte at any dose, but I made multiple attempts at it in 2014.

Dr Lerner found inverted T-waves, tachycardia and other heart abnormalities in his patients.

I have significant POTS on two TTT's (in 2014 and 2016) and had uncontrollable (sinus) tachycardia for several years, but did not have inverted T-waves on EKG like Dr. Lerner's patients. I had EKG's every year since 2013 but they never showed inverted T-waves and I asked my Cardio specifically b/c I was curious how I compared to Dr. Lerner's patients.

 

[Wonkmonk]

@Gingergrrl Thank you for taking the time to explain these points. I have been thinking for some time how your history of disease could fit in Dr Lerner's theory.

I think in your case, there is also the mold factor, which is known to trigger autoimmunity. I suspect it might have been plain and simple CFS after your mono, but it morphed into some kind of CFS plus autoimmunity mingle-mangle due to the mold exposure.

If I recall correctly the time when your positive EBV disappeared was when you were exposed to the mold and your autoimmunity was discovered shortly after that, right?

But overall, from our speculations, it is not surprising that Rituximab helps you, because if you have a EBV CFS problem plus a mold-triggered autoimmunity problem, Rituximab has two possible ways in which it could help you: first and foremost by killing the autoantibodies, but killing the EBV reservoir possibly helped, too.

I have to stress the evidence that these theories are in fact correct is very limited, it is for the most part speculation, but I think a lot of it adds up and that's why I think you have reason to be optimistic and expect a more pronounced recovery in the coming months.