Important Discovery Exposes Autoimmune Nature of ME/CFS – HERVs Implicated

February 20, 2013

by Joel (Snowathlete)

Plasmacytoid dendritic cell interacting with a T-cell.

Plasmacytoid dendritic cell interacting with a T-cell.

Some dates you remember forever.  Yesterday, on Wednesday 20th February 2013, a paper was published that may represent a major breakthrough in understanding the underlying mechanisms and cause of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

The paper, from long-time ME/CFS researchers Dr Kenny De Meirleir, Vincent Lombardi and other colleagues in association with the Whittemore Peterson Institute, reports findings that amount to ME being an autoimmune disease.

Dr Kenny De Meirleir is perhaps best known for the work he has done on the gut and its link to the pathophysiology of ME/CFS, so it is no surprise to hear that this latest finding is related to the major role of the lymphatic immune system in the gut. What will surprise some is that they have been able – despite its massive complexity – to narrow it down to a specific type of cell and to show how this cell ends up creating a state of autoimmunity in the body.

Prompted by reports of associations between other neuroinflammatory diseases and Human Endogenous Retrovirus (HERV) expression, De Meirleir and his team looked for the same type of occurrence in ME/CFS patients. Specifically, they looked in tissue from duodenum biopsies – the duodenum is at the top of the small intestine.

What is being reported?

The paper reports that the Plasmacytoid dendritic cells (pDCs) of eight out of 12 ME/CFS patients studied were found to be immunoreactive to antibodies against HERV proteins. In contrast no immunoreactivity was found in any of the eight controls.

All patients met both the Canadian and Fukuda criteria and were found to have substantial disruption of gut microbiota. Samples were from surplus de-identified clinical biopsies from previous ME patients.

pDCs are part of the innate immune system. They circulate in the blood but occur mostly within the secondary lyphoid organs, which is why they are present in the gut. pDCs are antigen-presenting cells that have a stimulatory role within the immune system. This immunoreactivity to HERV proteins was found uniquely in these pDC cells only. Dendritic cells have the potential to mistakenly identify something as an antigen when they shouldn’t, and this may be the cause of some autoimmunity.

HERVs are in our genome. We were born with them, and they are left over viral elements from ancient retroviruses that infected our ancestors’ germ line cells millions of years ago and stayed there passively, being replicated and passed on to new generations. They are abundant in our genome (5-8% – Robert Belshaw et al, 2004), but most, probably all, are defective due to mutations and deletions that have occurred in our genome over the millennia.  Unlike exogenous retroviruses such as HIV, HERVs are replication incompetent – so they’re not a moving target. Our understanding of HERVS is still undergoing change, and there is some evidence that some of this DNA – once thought to be nothing more than junk – actually contributes to our existence by performing various useful tasks within us (J-L Blond et al, 2000). It is known that these HERV elements in our DNA can and do express proteins, though normally they do not provoke a significant immune reaction.

The study reports that proteins found in the ME samples reacted with monoclonal antibodies to HERV proteins and that the immunoreactive cells were pDCs.

What checks did they make?

Positively, having found that the ME patient duoednum tissue was reacting to these HERV antibodies, De Meirleir and his team went a step further and checked to see whether murine retroviral antibodies would also cross react with the tissue – something which should occur if HERV proteins were present – and the results were again positive.

Finally, the team carried out further checks to rule out non-specific reaction and also tested stomach tissue from the same patients and controls, all of which came back negative, as expected.

Now they made efforts to determine exactly which cell types were immunoreactive to the HERV protein antibodies. Via a series of further tests the team hoped to whittle down the potential cell types. First they managed to zoom in on the hematopoietic cell lineage and then further sharpened the result to identify the cells as pDCs. They then double checked via a secondary means to confirm the result.

Having identified that the cells were pDCs, next they counted them and compared that count to the healthy controls. The ME patients were found to have approximately 4.7 times as many pDCs as the controls. Of the pDCs in the duodenum samples from ME patients, approximately 44 percent were found to be reactive to the HERV proteins.

Furthermore, in order to confirm that this was definitely a reaction to identifiable HERV proteins, the team sequenced both the RNA derived from the biopsy samples and from purified pDCs and found matching sequences from known HERVs. Although at this point they cannot definitively rule out that the immunoreaction seen was a result of an infectious exogenous retrovirus, as opposed to a HERV, their identification of matching HERV sequences argues strongly against this possibility.

So the cause of ME/CFS might be autoimmunity to HERVs?

As De Meirleir and his team point out, this would be the first time that an association between pDCs and HERVs has been shown to cause disease, though proven autoimmune diseases such as Multiple Sclerosis and Rheumatoid Arthritis have already been linked with pDC abnormalities and HERV involvement (G Freimanis et al).

The discussion section of the paper suggests that a number of immunological measurements reported in ME/CFS patients in the past, by various groups, may be a result of HERV involvement in pDCs, because pDCs are known to produce a variety of other immunological cells in abundance, such as interferon alpha, which modulates Natural Killer cell (NK) function. Low NK cell function is often associated with ME/CFS (Whiteside TL et al, 1998).

A lot is still unknown about HERVs, but they have been increasingly linked with disease. A study looking at HIV found that HERV expressed peptides were higher in HIV positive patients compared to controls and that T cells responded to these peptides (K E Garrison et al). A pair of studies looking at EBV showed that it could potentially activate retroviral elements in our DNA (Sutkowski et al, 2004 and 1996) and it’s possible that something similar could be going on here. Indeed the authors of this paper mention this previous finding and point out the long association between the disease and Herpes viruses, including De Meirleir’s previous discovery of herpes viruses in the duodenum of patients with ME/CFS (De Meirleir et al, 2009).

For most of us, immune dysfunction is a hallmark of ME/CFS, and several papers have reported specific immune dysfunction in the disease, particularly in the gut, highlighting the important role that the gut plays in maintaining health. For example, changes in the gut flora can result in incorrect function of the gut mucosal barrier (Shaheen E Lakham et al, 2010). Without these components of the immune system in our gut being correct, we are exposed to increased infection and inflammation and it is thought that this inflammation may be an aggravating factor as there is some evidence of inflammation increasing HERV protein expression and autoimmunity (Lee YK et al, 2011). 

What Next?

Replication. That’s what someone (we don’t know who yet) needs to do; someone has to replicate and confirm these findings in a bigger sample of patients. Or disprove them… 

We know from experience that we mustn’t get ahead of ourselves, and following replication comes more study because it would need to be confirmed that this was the cause of ME/CFS and not some knock-on effect unlinked to the pathogenesis of the disease, but if it checks out then we have a confirmed autoimmune disease and the certainty that goes with it.

We don’t understand autoimmune diseases that well yet, though this finding has the potential to revolutionize our understanding of autoimmunity. If confirmed then these findings could have repercussions for several other autoimmune diseases, particularly those with gastrointestinal dysfunction and neuroinflammation, such as MS, Lupus, and Crohn’s, whose cause may follow the same or a similar model. That would be good for everyone. Once again it seems ME/CFS has become sexy, just like it was when the XMRV saga began. Let’s hope this works out better in the long run…

If this research stands up then we are in a great position, because we already understand quite a bit about where the problem is happening. The bad thing about HERVs is that they’re immutable – they’re in our DNA and we can’t do much to change that. On the plus side, everyone has HERVs, so if they are linked with disease then it’s important to get to the bottom of how and why, for everybody’s sake.

Treatments for autoimmune diseases tend to be immune-modulating drugs to tone down the immune system’s effect and limit damage, and initial ‘treatment’ may also involve reducing gut inflammation. The theory is that if you can cut inflammation then you should get less autoimmune reaction, though that alone would be unlikely to fix the problem. 

It’s too early to talk about fixes – the first thing we need is for someone to confirm these findings…until then, hold fire…

A Reason to be Hopeful

If it works out then this discovery will be a breakthrough in understanding the cause and mechanisms of ME/CFS.  With that reality will come greater recognition, greater funding, greater focus, and ultimately – in the long run – treatments!

Of course none of this will happen overnight, we still have some way to go, but it could mean the beginning of the end, and we have waited for the end to this illness for so long.  We deserve this to work out. Don’t we? 

But you don’t always get what you deserve. Only time will tell if we remember Wednesday 20th February 2013 as a significant milestone on the long journey we are on to get to the bottom of this illness.

 

Joel was diagnosed with ME/CFS in 2009 but struggled with the illness for some time prior to this. He loves to write, and hopes to regain enough health to return to the career he loved and have his novels published.

 

REFERENCES

De Meirleir et al. 2013. Plasmacytoid Dendritic Cells in the Duodenum of Individuals Diagnosed with Myalgic Encephalomyelitis Are Uniquely Immunoreactive to Antibodies to Human Endogenous Retroviral Proteins. 2013.

Robert Belshaw et al. Long-term reinfection of the human genome by endogenous retroviruses. 2004

Jean-Luc Blond et al. An Envelope Glycoprotein of the Human Endogenous Retrovirus HERV-W Is Expressed in the Human Placenta and Fuses Cells Expressing the Type D Mammalian Retrovirus Receptor. 2000.

Sutkowski  N et al. Epstein-Barr Virus latent membrane protein LMP-2A is sufficient for transactivation of the Human Endogenous Retrovirus HERV-K18 superantigen. Journal of Virology. 2004.

G Freimanis et al. A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis. 2010.

Whiteside TL et al. Natural killer cells and natural killer cell activity in chronic fatigue syndrome. 1998.

K E Garrison et al. T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection. 2007.

Sutkowski  N et al. Virus-encoded superantigens. Microbiological Reviews. 1996.

De Meirleir et al. Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients. 2009.

Shaheen E Lakhan et al. Gut inflammation in chronic fatigue syndrome. 2010.

Lee YK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. 2011.

 

 

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89 comments

{ 89 comments… read them below or add one }

Sherezade February 20, 2013 at 10:01 pm

Wow Joel, you are on top of everything! Thank you for keeping us updated. ;)

Is curious because i've spent the whole day researching for autoinmune syndromes, because i just got tested for that. That was the only test that my infectologist allowed me to run, based on my symptoms.

Anyway, every night before going to bed i pray to God to give the scientifics and the doctors, the wisdom to find the true about this disease and the right treatment. No one deserves this. Articles like yours gives me some hope though.

alex3619 February 20, 2013 at 10:18 pm
5150 February 20, 2013 at 11:38 pm

Re "autoimmune" : how does the very obvious fact(in my cohort anyway) that CFS/ME is Contagious , fit into the HERV implicated theory? I was fine until I was exposed to someone else's really powerful and bad HERV? Because I was just great until that event, after which my life went to hell. So there's an extremely virile contagious HERV out there? and where did it come from? indigenous somewhere? or what. Thanks.

Mya Symons February 20, 2013 at 11:51 pm

Very interesting article. Thank you. I am wondering a couple things after reading this. 1st, do these antibodies to HERV's have any connection to the strange B-Cell blood test results some of us have (a lot of immature B-Cells and too low a number of mature B-Cells)? 2nd, are these antibodies responsible for some of the confusion with the Mikovitz, Lombardi etc. XMRV studies. Did they mistake these antibodies for a current unknown retroviral infection (in this case XMRV)? Finally, and this is far fetched, is it possible that a person who has many antibodies to several different types and fragments of HERV's could be immune to HIV (as in the immune system would recognize the virus as an infectious retrovirus before it had time to hide and replicate)?

Valentijn February 21, 2013 at 12:44 am
5150

Re "autoimmune" : how does the very obvious fact(in my cohort anyway) that CFS/ME is Contagious , fit into the HERV implicated theory? I was fine until I was exposed to someone else's really powerful and bad HERV? Because I was just great until that event, after which my life went to hell. So there's an extremely virile contagious HERV out there? and where did it come from? indigenous somewhere? or what. Thanks.

Autoimmune disease is likely to be triggered in some cases by viruses – such as Coxsackie B being implicated in Type I Diabetes. It's a matter of correlation thus far (more type I diabetics than non-diabetics have had the virus), but it's pretty suggestive.

Valentijn February 21, 2013 at 12:45 am

Great article, snowathlete – going to link to it so my friends and family have something more comprehensible than the actual research paper to read :D

Allyson February 21, 2013 at 1:28 am

THanks for the article; lymph is also a connective tissue so it may be just part of the picture where all connective tissue is affected- including the gut… hence immune system involvement.
There are some who think it is a genetiic condition, so in addition to ymphatic involvement the blood vesssels are also defective and do not constrict adequately to return blood to the brain and heart..
see this link for more

http://forums.phoenixrising.me/index.php?threads/is-me-due-to-ehelrs-danlos-syndrome-stretchy-veins.20351/#post-310872

Kati February 21, 2013 at 1:30 am
5150

Re "autoimmune" : how does the very obvious fact(in my cohort anyway) that CFS/ME is Contagious , fit into the HERV implicated theory? I was fine until I was exposed to someone else's really powerful and bad HERV? Because I was just great until that event, after which my life went to hell. So there's an extremely virile contagious HERV out there? and where did it come from? indigenous somewhere? or what. Thanks.

Well 5150, this research provides another piece of the puzzle, and providing more reasons
1) for governments to fund research for ME,
2) for researchers especially in virology and immunology, to be interested in researching us and push a bit further
3) for physicians to get interested in our disease this much more
4) for patients to be willing to give a piece of their duodenum for research!!!! :-)

lansbergen February 21, 2013 at 3:45 am
Mya Symons

2nd, are these antibodies responsible for some of the confusion with the Mikovitz, Lombardi etc. XMRV studies. Did they mistake these antibodies for a current unknown retroviral infection (in this case XMRV)?

8 out of 12 is 67% if I am not mistaken. Same procent as the Lombardi study. Makes me wonder.

The authers say they can not exclude an exogenous retro.

Not the Silverman XMRV but maybe another exogenous.

Anyway retro's are back in the picture and there is a lot of work to do to solve the mistery.

lansbergen February 21, 2013 at 3:47 am
5150

Re "autoimmune" : how does the very obvious fact(in my cohort anyway) that CFS/ME is Contagious , fit into the HERV implicated theory? I was fine until I was exposed to someone else's really powerful and bad HERV? Because I was just great until that event, after which my life went to hell. So there's an extremely virile contagious HERV out there? and where did it come from? indigenous somewhere? or what. Thanks.

HERVs can be activated by another infection.

ana_bxl February 21, 2013 at 3:58 am

Joel………..THANKS A LOT for explaining it to us in "normal language" :O) THANKS,THANKS A LOT!

taniaaust1 February 21, 2013 at 4:00 am

Its sad thou that govs will probably need to see a big part of the ME puzzle before they ever will get serious with funding it. But while its all in the too hard basket.. they dont want to fund.

There are some who think it is a genetiic condition

I think this discovery would explain the genetic link too.. as after all we are inheriting that so call junk "HERV" DNA from our parents so would have similar DNA.

Re "autoimmune" : how does the very obvious fact(in my cohort anyway) that CFS/ME is Contagious

Sounds like we may be giving others our secondary co-existing viruses we pick up due to having this.. which in turn could go and actiivate this HERV issue in them too. So an interplay happening between HERV and other viral things be in EBV or whatever.

I suspect I carry some reacitiving viral things and have issues with what appears to be herpes inside my mouth at times. (I wouldnt be surprised if I have reactiving EBV happening too). Im also carry antibodies to CMV and toxoplasmosis.. so I wouldnt doubt I have reactiving stuff which could trigger something off in others and make them vulerable to the HERV stuff.

taniaaust1 February 21, 2013 at 4:02 am

Oh and thanks Joel.

I didnt think I'd ever see anyone write a medical article as well as Cort does, when it comes to bridging things and making the medical stuff more easy to understand. You've just filled a big gap ive had with this site since Cort left.

Valentijn February 21, 2013 at 4:42 am
lansbergen

8 out of 12 is 67% if I am not mistaken. Same procent as the Lombardi study. Makes me wonder.

The authers say they can not exclude an exogenous retro.

Not the Silverman XMRV but maybe another exogenous.

Anyway retro's are back in the picture and there is a lot of work to do to solve the mistery.

These current results also might explain the prior XMRV results that weren't replicated. The impression I got is that the current results, if indicating an immune reaction to an HERV protein, could explain a false positive showing up for XMRV due to the cross-reactivity. WPI's involvement therefore might have been based on their previous findings being wrong, but then looking at how those false positives could have been produced.

lansbergen February 21, 2013 at 5:38 am
Valentijn

WPI's involvement therefore might have been based on their previous findings being wrong, but then looking at how those false positives could have been produced.

Yep

Gijs February 21, 2013 at 5:44 am

i think this finding is the result of the autonomic overdrive i.e. abnormal stressrespons started by (nor) adrenaline. This finding does not fit in a causal model.

lansbergen February 21, 2013 at 6:09 am
Gijs

i think this finding is the result of the autonomic overdrive i.e. abnormal stressrespons started by (nor) adrenaline. This finding does not fit in a causal model.

I disagree

beaverfury February 21, 2013 at 6:30 am

Is it true to say all autoimmune conditions can only be managed, and not cured?

snowathlete February 21, 2013 at 6:34 am
Sherezade

Wow Joel, you are on top of everything! Thank you for keeping us updated. ;)

Is curious because i've spent the whole day researching for autoinmune syndromes, because i just got tested for that. That was the only test that my infectologist allowed me to run, based on my symptoms.

Anyway, every night before going to bed i pray to God to give the scientifics and the doctors, the wisdom to find the true about this disease and the right treatment. No one deserves this. Articles like yours gives me some hope though.

You're welcome. I'm glad you liked it. I'm keeping an eye on your thread about your autoimmune results – very interesting. I wonder how many of us have undergone similar tests?

Gijs February 21, 2013 at 6:38 am

In addition, I think that researchers like Lombardi and the WPI after the XMRV debacle not be taken seriously. I hope for those researchers that at least the research is carried out professionally this time. This model (HERV) does not explain the symptoms and findings by other researchers. How and what is infected in de nervous system that explains the chronic overstimulated autonomic part or the abnormal stressrespons by (HERV). It makes no sense. I am not so optimistic. It is one of the many abnormalities.

snowathlete February 21, 2013 at 7:01 am
Mya Symons

Very interesting article. Thank you. I am wondering a couple things after reading this. 1st, do these antibodies to HERV's have any connection to the strange B-Cell blood test results some of us have (a lot of immature B-Cells and too low a number of mature B-Cells)? 2nd, are these antibodies responsible for some of the confusion with the Mikovitz, Lombardi etc. XMRV studies. Did they mistake these antibodies for a current unknown retroviral infection (in this case XMRV)? Finally, and this is far fetched, is it possible that a person who has many antibodies to several different types and fragments of HERV's could be immune to HIV (as in the immune system would recognize the virus as an infectious retrovirus before it had time to hide and replicate)?

Thanks Mya, glad you liked it.
Good questions!
1. In short; yes. But, we dont know exactly what is happening here yet. If something is not right with the pDCs then that will affect a lot of the other immune cells in consequnce.
2. Maybe. It would explain a lot wouldn't it.
3. Um. HIV immunity isn't my area of knowledge – however, I am aware that people with HIV have higher HERV proteins, and researchers are wondering if they can use this as a means of targeting HIV. The problem with HIV (well not the only problem, obviously…) is that it mutates so rapidly so therapys to kill it dont work. The hope is the they may be able to target HIV via the HERV proteins. I dont know the specifics of that, but I read something along those lines.

To elaborate more on your question – I wonder (and this is speculation) whether HERVs in our genome is not really a random accident, but rather some kind of positive mechanism to pass on information on viruses to the next generation, to help with immunity.

lansbergen February 21, 2013 at 7:04 am
Gijs

. This model (HERV) does not explain the symptoms and findings by other researchers. How and what is infected in de nervous system that explains the chronic overstimulated autonomic part or the abnormal stressrespons by (HERV). It makes no sense. I am not so optimistic. It is one of the many abnormalities.

It fits my hypothese and can be caused by the pathogen I always suppected. Still no test for that pathogen for living patients.

For the record that is not herpes.

lansbergen February 21, 2013 at 7:11 am
beaverfury

Is it true to say all autoimmune conditions can only be managed, and not cured?

Levemisole decreases autoantibodies in several diseases .

I think if the causing pathogen can be eliminated the disease will vanish.

Gijs February 21, 2013 at 7:41 am

I know it is not herpes. But this researchers suggest that herpes 4 and 6 can be an important modulator of HERV-k18. Quote: ''Dr. Bridget Huber showed that HERV-K18 expression could be induced by herpes viruses such as Epstein-Barr virus and human herpes virus 6 (HHV-6) (34,61). Consistent with that work and with the data presented here, both of these viruses have been observed in the duodenum of individuals with ME (62)''. This is not correct according to recent research done by Komaroff et. al. Clin Infect Dis. 2013 Feb 13. [Epub ahead of print]
Human Endogenous Retrovirus-K18 Superantigen Expression and Human Herpesvirus-6 and Human Herpesvirus-7 Viral Loads in Chronic Fatigue Patients.
Oakes B, Hoagland-Henefield M, Komaroff AL, Erickson JL, Huber BT.

snowathlete February 21, 2013 at 7:54 am
Valentijn

Great article, snowathlete – going to link to it so my friends and family have something more comprehensible than the actual research paper to read :D

Thanks Val. Glad you liked it, and good idea telling friends and family. Most don't have time to read the whole paper and digest it, but it's worth them hearing about.

ana_bxl

Joel………..THANKS A LOT for explaining it to us in "normal language" :O) THANKS,THANKS A LOT!

You're more than welcome ana!

taniaaust1

Oh and thanks Joel.

I didnt think I'd ever see anyone write a medical article as well as Cort does, when it comes to bridging things and making the medical stuff more easy to understand. You've just filled a big gap ive had with this site since Cort left.

Thanks tania. Those are big shoes to fill, so if I'm filling them, even in part, then that's praise indeed!

snowathlete February 21, 2013 at 8:05 am
Gijs

I know it is not herpes. But this researchers suggest that herpes 4 and 6 can be an important modulator of HERV-k18. Quote: ''Dr. Bridget Huber showed that HERV-K18 expression could be induced by herpes viruses such as Epstein-Barr virus and human herpes virus 6 (HHV-6) (34,61). Consistent with that work and with the data presented here, both of these viruses have been observed in the duodenum of individuals with ME (62)''. This is not correct according to recent research done by Komaroff et. al. Clin Infect Dis. 2013 Feb 13. [Epub ahead of print]
Human Endogenous Retrovirus-K18 Superantigen Expression and Human Herpesvirus-6 and Human Herpesvirus-7 Viral Loads in Chronic Fatigue Patients.
Oakes B, Hoagland-Henefield M, Komaroff AL, Erickson JL, Huber BT.

The Komaroff study was only looking at HERV-18 though, and only in the blood and saliva. It doesn't rule out other HERVs and it doesn't rule out the problem being in the gut – specifically the duodenum. It also didnt look for EBV (HHV-4), which surprised me – given the previous studies, why not look for that too?

Gijs February 21, 2013 at 8:18 am

The findings of Kenny et. al. are not specific to ME. These are also found in other diseases. This study again showed no breakthrough.

acer2000 February 21, 2013 at 11:31 am

Maybe I'm missing something here. This is an interesting finding suggesting that HERVs may be present/activated in some people with symptoms of ME. But what does it have to do with auto-immunity?

snowathlete February 21, 2013 at 11:57 am
beaverfury

Is it true to say all autoimmune conditions can only be managed, and not cured?

Existing treatments tend to be about management and limiting damage by supressing the immune system. There are new treatments being developed for autoimmune diseases though that show promise. Here is an interesting article about just one of the many things that people are trying out in MS. This could work as a cure, in theory, though it is early days.

It still is not well understood what triggers autoimmunity in the first place. If we understood that then we would be able to develop better treatments and maybe even cures, as well as preventative measures. One theory is that HERVs are involved and there is growing evidence for this. But it is complicated further because even if that is right, you then have to answer the question of what triggered the problem with the HERVs? One theory is that viruses might be that trigger, and some evidence has already been collected to show that EBV could be one such virus. The good thing is that depending on the actual mechanism, one finding in any one autoimmune disease could have positive implications for understanding other autoimmune diseases.

Having an autoimmune disease would not be great, but it is better than having an autoimmune disease (or any other type of disease for that matter) and not knowing it, the illness being misunderstood and neglected etc.

Valentijn February 21, 2013 at 12:25 pm
acer2000

Maybe I'm missing something here. This is an interesting finding suggesting that HERVs may be present/activated in some people with symptoms of ME. But what does it have to do with auto-immunity?

HERVs are present in everyone … it's part of the human DNA. The issue is that we seem to have an immune reaction to a protein produced by HERVs. Since it's part of our DNA, reacting to it would be auto-immune.

Ema February 21, 2013 at 12:40 pm
beaverfury

Is it true to say all autoimmune conditions can only be managed, and not cured?

There is some (limited) evidence and ongoing studies using IgG therapy to reverse autoimmune conditions. Many of the people I know on Hizentra (sub Q IgG) have had substantial reductions in the number of autoantibodies present.

The doses used are generally higher than for IgG replacement therapy. And of course, since it is not FDA approved for this purpose, generally impossible to get from a financial standpoint unless you have a concurrent primary immunodeficiency disease (which is not out of the realm of possibility for many of us). I was luckily able to qualify for Hizentra through their patient assistance program.

Ema

Legolas February 21, 2013 at 12:48 pm
acer2000

Maybe I'm missing something here. This is an interesting finding suggesting that HERVs may be present/activated in some people with symptoms of ME. But what does it have to do with auto-immunity?

I gonna quote from the article;

HERV proteins and serum antibodies against HERV's have been associated with a number of autoimmune diseases, including MS and SLE.
… it is widely believed that the humoral immune response against HERV proteins leads to autoimmunity through a process of molecular mimicry. HERV proteins are known to act as superantigens.

So the antibodies that you make to attack HERV proteins also (accidently) attack other cells/parts in the body.
At least, this is how is see it.

Leachim February 21, 2013 at 1:14 pm

Thank you, Joel, for a very well written article!

As a comment to some of the comments: From what I know from different sources De Meirleir (I'm a patient of his) doesn't think this autoimmune reaction is the cause of ME, rather one of the later consequences of the disease process, the cause of disabling symptoms though, and probably also a factor in upholding the web of interacting pathological processes. De Meirleir's model of the disease process starts with disruptions in the gut flora causing an array of immune dysfunctions, and I suppose the autoimmunity should be one of the consequences of some parts of the immune system being hyperactive (parts of the innate immune system and Th2/the b-cells).

Gijs February 21, 2013 at 1:32 pm
Leachim

Thank you, Joel, for a very well written article!

As a comment to some of the comments: From what I know from different sources De Meirleir (I'm a patient of his) doesn't think this autoimmune reaction is the cause of ME, rather one of the later consequences of the disease process, the cause of disabling symptoms though, and probably also a factor in upholding the web of interacting pathological processes. De Meirleir's model of the disease process starts with disruptions in the gut flora causing an array of immune dysfunctions, and I suppose the autoimmunity should be one of the consequences of some parts of the immune system being hyperactive (parts of the innate immune system and Th2/the b-cells).

The immune system is hyperactive because the stressrepons or autonomic nervous system is hyperactive; (nor) adrenaline-cortisol-immune system etc… the problem is in the CNS. NOT DUE TO PSYCHOSOCIAL STRESS BUT BECAUSE THE SYSTEM IS BROKEN.

Forebearance February 21, 2013 at 2:37 pm

I don't understand what this means:
"The paper reports that the Plasmacytoid dendritic cells (pDCs) of eight out of 12 ME/CFS patients studied were found to be immunoreactive to antibodies against HERV proteins. "

What does it mean to be immunoreactive to antibodies against HERV proteins?
Can someone put it into plainer English for me?
Thank you!!!

Also, I wonder how this study would relate to Dr. Jamie Deckoff-Jones' theory that we are getting retrovirus fragments from vaccines which are completing or activating HERVs. Apologies to her if I'm not stating her theory correctly.

snowathlete February 21, 2013 at 3:38 pm
Forebearance

I don't understand what this means:
"The paper reports that the Plasmacytoid dendritic cells (pDCs) of eight out of 12 ME/CFS patients studied were found to be immunoreactive to antibodies against HERV proteins. "

What does it mean to be immunoreactive to antibodies against HERV proteins?
Can someone put it into plainer English for me?
Thank you!!!

Also, I wonder how this study would relate to Dr. Jamie Deckoff-Jones' theory that we are getting retrovirus fragments from vaccines which are completing or activating HERVs. Apologies to her if I'm not stating her theory correctly.

Hi Forebearance, I should have gone over this in the article really, sorry.
What they did was Immunohistochemistry. You can read about that here on wikipedia. They apply a solution of antibodies (in this case HERV antibodies) to the tissue and they have been conjugated with enzymes that show up a color if there is a reaction (if the antibodies find the expected antigen that they are looking for (in this case HERVs). You can see in the actual paper the photographs of the tissue with colored cells where it has reacted (pages 4, 5 and 6).

The vaccine link is an interesting one. Not sure but its potentially possible. Its widely accepted (i think) that we do have antibodies to various animal tissue in our bodies as a result of medications and vaccines developed using animals. Doesn't get talked about much for some reason. I always thought it was quite remarkable!

Sushi February 21, 2013 at 3:53 pm
snowathlete

Hi Forebearance, I should have gone over this in the article really, sorry.
What they did was Immunohistochemistry. You can read about that here on wikipedia. They apply a solution of antibodies (in this case HERV antibodies) to the tissue and they have been conjugated with enzymes that show up a color if there is a reaction (if the antibodies find the expected antigen that they are looking for (in this case HERVs). You can see in the actual paper the photographs of the tissue with colored cells where it has reacted (pages 4, 5 and 6).

The vaccine link is an interesting one. Not sure but its potentially possible. Its widely accepted (i think) that we do have antibodies to various animal tissue in our bodies as a result of medications and vaccines developed using animals. Doesn't get talked about much for some reason. I always thought it was quite remarkable!

I can't add to the scientific discussion but just want to thank Joel for writing this article. It is very helpful when you put it along side the published article. So Thanks! :thumbsup:

Sushi

liquid sky February 21, 2013 at 6:07 pm
lansbergen

Levemisole decreases autoantibodies in several diseases .

I think if the causing pathogen can be eliminated the disease will vanish.

Where can you obtain Levamisole, lansbergen? I know it is used to treat worms in animals, but I have not been able to find it anywhere.

serg1942 February 21, 2013 at 6:39 pm

Hello to everybody,
As many of you, I'm trying to fully understand the mechanism proposed in the recent publish paper from KDM et al.

I've read all your comments and reports, and they are great, but they seem not to address a few issues that for me, are the most important things to understand. So, I am going to write down the questions that I am not able to solve, with the target of being able to explain in very simple words the proposed mechanism, mainly for the Spanish CFS community, who mostly does not manage in English, and are eager to know what is all this about.
The whole study is very well summarized here:

http://phoenixrising.me/archives/16017
(thank you Joel for the great article!)

Questions:
My goal is to complete /correct the following sketch:
http://www.sfc-em-investigacion.com/download/file.php?id=236&mode=view
(it's just an ugly-fast made drawing I made while reading the article and researching, but it'll be "nicer" when finished! :)

pDCells express HERVs genome, transcribing HERVs' proteins (gag and env). They don't say, but I assume that they go to the cytoplasm after being transcribed, where they may act as superantigents, that after being processed by phagocytosis will create the HLA-DR (MHC II) membrane receptor, that distinguishes the Antigen Presenting Cells from the rest (APCs). But this process is carried out in an abnormal way, so that the Lymphocytes T that stick onto these receptors in order to be activated, and thus are"told" what antigen to attack, are improperly and non-specifically activated. A lot of lymphocytes are activated by this way, then they activate in turn lymphocytes B that will synthesize antibodies against HERVs's proteins.
2- Where do these antibodies go?:

a- To the cell membrane of the pDCs? If so, do they die, or are just wrecked as a response, b/c the lymphocytes attacking those antibodies are not efficient due to the "non-especific activation"? The immunohistochemical assay shows that only pDCs shown reactivity against HERV proteins, so the only way this can happen (that I know), is if in their membrane, they express antibodies against HERV proteins. To my knowledge, this may happen independently of whether gaga and env proteins are only inside the cell or also in the serum.

b- To the HERV proteins, provided they go out of the cell. Do they? this is important in the sense that these proteins could travel throughout the whole body, so, they could be attacked in any place, explaining a systemic immune activation: systemic inflammation, coming from the gut! (this is the main idea…).

c- To ANY free protein in serum or inside cells that resembles the HERVs' proteins. This is the basis of molecular mimicry, and this is actually the way that it's proposed for the origin of autoimmunity, that is, lymphocytes and other members of the acquired response would attacked self proteins or self cells, in ANY part of the body.

Moreover, if we have a bunch of Lymphocytes "trained" to attack ANYTHING with antobodies against HERVs' proteins, they would attack ANY cell expressing these proteins…

So, in short, based on the above, this is my main question:

Where do the antibodies against HERVs' proteins go?, and what would be the exact process by which they are responsible for the autoimmunity? (Some of the possibilities I have listed above? A combination?)

2- Last question: they explain that the humoral response (Th2) against the HERVs' proteins leads to autoimmunity through molecular mimicry. Ok, the process I have described, if I have got it correctly would be exactly this, what would explain a shift of Th1 to Th2. So then, we would have two pathways that could cause symptomatology:

- Deffective Th1 response b/c of improperly activated lymphocytes T, and
- Excess Th2 response by the process I've explained of molecular mimicry involving antibodies anti- HERV proteins, and directly by the effect of dysrupted pDCs: low NKs, inflamation, etc.

So, the last quesion: What are the mechanism that wrecks the normal function of pDCs in the first place? I have assumed there may be two ways: 1- the improper Antigen Presentation process and 2- the attack of pDCs by lymphocytes.

I would really appreciate if any of you could help me with all this questions. More than one brain think better than only one (especially if layman and brain fogged!).

I, of course, do not have the knowledge to understand all this on my own, and would like to apologize beforehand for taking the risk of trying to understand things that are beyond my knowledge (that's why I'm asking to more expert people).

Thanks in advance for your insights!
Sergio

PS. I'm a CFS patient myself, student of medicine, vice-president of a National spanish association of people affected by mercury from amalgam fillings (including many PWCFS), and collaborator with many ME/CFS associations and institutions.

Ema February 21, 2013 at 6:52 pm
lansbergen

Levemisole decreases autoantibodies in several diseases .

I think if the causing pathogen can be eliminated the disease will vanish.

Are you sure levamisole decreases autoantibodies? I thought it was the opposite.

Ema

serg1942 February 21, 2013 at 6:55 pm

Hello to everybody,

As many of you, I'm trying to fully understand the mechanism proposed in the recent publish paper from KDM et al.

I've read all your comments and reports, and they are great, but they seem not to address a few issues that for me, are the most important things to understand. So, I am going to write down the questions that I am not able to solve, with the target of being able to explain in very simple words the proposed mechanism, mainly for the Spanish CFS community, who mostly does not manage in English, and are eager to know what is all this about.
The whole study is very well summarized here:

http://phoenixrising.me/archives/16017
(thank you Joel for the great article!)

Questions:

My goal is to complete /correct the following sketch:
http://www.sfc-em-investigacion.com/download/file.php?id=236&mode=view
(it's just an ugly-fast made drawing I made while reading the article and researching, but it'll be "nicer" when finished! :)

pDCells express HERVs genome, transcribing HERVs' proteins (gag and env). They don't say, but I assume that they go to the cytoplasm after being transcribed, where they may act as superantigents, that after being processed by phagocytosis will create the HLA-DR (MHC II) membrane receptor, that distinguishes the Antigen Presenting Cells from the rest (APCs). But this process is carried out in an abnormal way, so that the Lymphocytes T that stick onto these receptors in order to be activated, and thus are"told" what antigen to attack, are improperly and non-specifically activated. A lot of lymphocytes are activated by this way, then they activate in turn lymphocytes B that will synthesize antibodies against HERVs's proteins.

2- Where do these antibodies go?:

a- To the cell membrane of the pDCs? If so, do they die, or are just wrecked as a response, b/c the lymphocytes attacking those antibodies are not efficient due to the "non-especific activation"? The immunohistochemical assay shows that only pDCs shown reactivity against HERV proteins, so the only way this can happen (that I know), is if in their membrane, they express antibodies against HERV proteins. To my knowledge, this may happen independently of whether gaga and env proteins are only inside the cell or also in the serum.

b- To the HERV proteins, provided they go out of the cell. Do they? this is important in the sense that these proteins could travel throughout the whole body, so, they could be attacked in any place, explaining a systemic immune activation: systemic inflammation, coming from the gut! (this is the main idea…).

c- To ANY free protein in serum or inside cells that resembles the HERVs' proteins. This is the basis of molecular mimicry, and this is actually the way that it's proposed for the origin of autoimmunity, that is, lymphocytes and other members of the acquired response would attacked self proteins or self cells, in ANY part of the body.
Moreover, if we have a bunch of Lymphocytes "trained" to attack ANYTHING with antobodies against HERVs' proteins, they would attack ANY cell expressing these proteins…

So, in short, based on the above, this is my main question:

Where do the antibodies against HERVs' proteins go?, and what would be the exact process by which they are responsible for the autoimmunity? (Some of the possibilities I have listed above? A combination?)

2- Last question: they explain that the humoral response (Th2) against the HERVs' proteins leads to autoimmunity through molecular mimicry. Ok, the process I have described, if I have got it correctly would be exactly this, what would explain a shift of Th1 to Th2. So then, we would have two pathways that could cause symptomatology:

- Deffective Th1 response b/c of improperly activated lymphocytes T, and

- Excess Th2 response by the process I've explained of molecular mimicry involving antibodies anti- HERV proteins, and directly by the effect of dysrupted pDCs: low NKs, inflamation, etc.

So, the last quesion: What are the mechanism that wrecks the normal function of pDCs in the first place? I have assumed there may be two ways: 1- the improper Antigen Presentation process and 2- the attack of pDCs by lymphocytes.

I would really appreciate if any of you could help me with all this questions. More than one brain think better than only one (especially if layman and brain fogged!).

I, of course, do not have the knowledge to understand all this on my own, and would like to apologize beforehand for taking the risk of trying to understand things that are beyond my knowledge (that's why I'm asking to more expert people).

Thanks in advance for your insights!
Sergio

Helene February 21, 2013 at 9:00 pm

Hello everyone. I brought this up before: ok, viruses, but so many of kdm's patients are testing positive for borrelia. This is not a virus. It's the result of a tick.

How does this connect to all this?

Or is it that we all have borrelia from time immemorial and our immune system keeps it down, and when sick with CFS-me, the latent infection surfaces.

I am having some difficulty with this, particularly having seen folks with true Lyme.

lansbergen February 22, 2013 at 3:31 am
Mya Symons February 22, 2013 at 3:34 am
snowathlete

Thanks Mya, glad you liked it.
Good questions!
1. In short; yes. But, we dont know exactly what is happening here yet. If something is not right with the pDCs then that will affect a lot of the other immune cells in consequnce.
2. Maybe. It would explain a lot wouldn't it.
3. Um. HIV immunity isn't my area of knowledge – however, I am aware that people with HIV have higher HERV proteins, and researchers are wondering if they can use this as a means of targeting HIV. The problem with HIV (well not the only problem, obviously…) is that it mutates so rapidly so therapys to kill it dont work. The hope is the they may be able to target HIV via the HERV proteins. I dont know the specifics of that, but I read something along those lines.

To elaborate more on your question – I wonder (and this is speculation) whether HERVs in our genome is not really a random accident, but rather some kind of positive mechanism to pass on information on viruses to the next generation, to help with immunity.

Thank you for taking the time to answer my questions.

maryb February 22, 2013 at 5:04 am
Helene

Hello everyone. I brought this up before: ok, viruses, but so many of kdm's patients are testing positive for borrelia. This is not a virus. It's the result of a tick.

How does this connect to all this?

Or is it that we all have borrelia from time immemorial and our immune system keeps it down, and when sick with CFS-me, the latent infection surfaces.

I am having some difficulty with this, particularly having seen folks with true Lyme.

Helene – I've tested negative for Borrelia via KdM – dont know what the actual %age of his patients test positive.

Helene February 22, 2013 at 7:57 am
maryb

Helene – I've tested negative for Borrelia via KdM – dont know what the actual %age of his patients test positive.

Good morning to you all,
Well, I was tested at igenex, and neuroscience and these were inconclusive. KDM tested and I was negative ( twice). He suggested infectolabs, and it came out positive. I know of several other folks in this category.

maryb February 22, 2013 at 8:19 am
Helene

Good morning to you all,
Well, I was tested at igenex, and neuroscience and these were inconclusive. KDM tested and I was negative ( twice). He suggested infectolabs, and it came out positive. I know of several other folks in this category.

Thanks very interesting – seems that some lab testing is a waste of time then? Were your first tests with KdM done at Redlabs?

Ema February 22, 2013 at 9:21 am

I

lansbergen

Some links

http://www.ncbi.nlm.nih.gov/pubmed/21621152

http://www.ncbi.nlm.nih.gov/pubmed/447410

http://www.ncbi.nlm.nih.gov/pubmed/366145

http://www.ncbi.nlm.nih.gov/pubmed/7913970

more links

http://www.ncbi.nlm.nih.gov/pubmed/21497280

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1541217/

http://www.ncbi.nlm.nih.gov/pubmed/71868

I wonder how to reconcile those older abstracts with the reports in the past two years about levamisole causing increased autoimmune skin diseases when it was used as an adjuvant in cocaine. They seem to be contradictory.

http://medicine.ucsf.edu/news/fom/frontiers.html?key=5

Either way, levamisole sure sounds like nasty stuff. I'd like a way to reduce autoantibodies but wouldn't touch this stuff with a ten foot pole!

Thanks for the links!

lansbergen February 22, 2013 at 9:34 am
Ema

I
I wonder how to reconcile those older abstracts with the reports in the past two years about levamisole causing increased autoimmune skin diseases when it was used as an adjuvant in cocaine. They seem to be contradictory.!

Low dosis and high dosis have opposite effects.

Helene February 22, 2013 at 10:39 am
maryb

Thanks very interesting – seems that some lab testing is a waste of time then? Were your first tests with KdM done at Redlabs?

Hi,
In 2009 dec. I was tested at igenex. On the basis of that a couple of doctor's suggested possibility of Lyme, but the tests were inconclusive really. Then in 2011 and 2012 I was tested at redlabs, and the tests were negative. KDM suggested the lab in Germany. These tests were done relatively recently, and they came out positive with an active infection. I present as classic CFS.

I really do not know how to put all this together. Several KDM patients who were classified as ME are now positive for borrelia and/or other associated confections.

If anyone can shed any light, please do

snowathlete February 22, 2013 at 11:33 am
Helene

Hello everyone. I brought this up before: ok, viruses, but so many of kdm's patients are testing positive for borrelia. This is not a virus. It's the result of a tick.

How does this connect to all this?

Or is it that we all have borrelia from time immemorial and our immune system keeps it down, and when sick with CFS-me, the latent infection surfaces.

I am having some difficulty with this, particularly having seen folks with true Lyme.

Hi Helene,
There is a lot we don't know yet, but I find it very interesting that plenty of people test positive for Lyme, often patients are very surprised, often they have had negative results previously.
I have lots of thoughts on Lyme and Borrelia and am going to be covering it in my next Zoonotics article (here is the intro to that series). There is a lot to talk about there and plenty of research papers for me to read through first.
It is not impossible for Lyme/Borrelia to be a cause or a component of ME/CFS. We have not done enough to rule it out yet, though we have taken some steps on that road, which is good. On the other hand some people may have Lyme, but think that they have ME/CFS. Everyone should be tested in my view. How much and what tests is still something I am researching. Finally, there is no rule to say that someone with ME/CFS cannot have Lyme/Borrelia as a coinfection, even if it is not a cause of their ME/CFS, and given the immune disfunction in ME/CFS that may be a reason why some people cant get over Lyme even when treated.

Similar story with other infections like Bartonella, Babesia etc.

anniekim February 22, 2013 at 2:42 pm
Helene

Hi,
In 2009 dec. I was tested at igenex. On the basis of that a couple of doctor's suggested possibility of Lyme, but the tests were inconclusive really. Then in 2011 and 2012 I was tested at redlabs, and the tests were negative. KDM suggested the lab in Germany. These tests were done relatively recently, and they came out positive with an active infection. I present as classic CFS.

I really do not know how to put all this together. Several KDM patients who were classified as ME are now positive for borrelia and/or other associated confections.

If anyone can shed any light, please do

Helene, may I ask did you do the western blot igg and igm at Infectolab or the Ltt elispot, or perhaps both? I did the ltt elispot at infectolab which came out negative. Don't know whether should do the western blot too to be sure, just more money to pay out…

anniekim February 22, 2013 at 3:00 pm

For example, changes in the gut flora can result in incorrect function of the gut mucosal barrier (Shaheen E Lakham et al, 2010). Without these components of the immune system in our gut being correct, we are exposed to increased infection and inflammation and it is thought that this inflammation may be an aggravating factor as there is some evidence of inflammation increasing HERV protein expression and autoimmunity (Lee YK et al, 2011).

Is this suggesting that if the changes in the gut flora are corrected (I take it gut flora changes means too much bad bacteria?) this could bring benefit/resolve the subsequent immune problems? is this why some find correcting gut helpful? is it suggested that gut treatments are important?

Leachim shared above that 'De Meirleir's model of the disease process starts with disruptions in the gut flora causing an array of immune dysfunction'. Does KDM believe then if the gut is treated at the start of the illness the downstream processes can be stopped and these few patients if caught early enough can make good recoveries? I know of one young woman who hadn't been ill for long, saw kdm, followed his gut treatments and made a full recovery. Dont know whether it lasted. Know others ill longer, saw KDM, did his gut treatments with little to no benefit.

Forebearance February 22, 2013 at 3:31 pm
snowathlete

Hi Forebearance, I should have gone over this in the article really, sorry.
What they did was Immunohistochemistry. You can read about that here on wikipedia. They apply a solution of antibodies (in this case HERV antibodies) to the tissue and they have been conjugated with enzymes that show up a color if there is a reaction (if the antibodies find the expected antigen that they are looking for (in this case HERVs). You can see in the actual paper the photographs of the tissue with colored cells where it has reacted (pages 4, 5 and 6).

The vaccine link is an interesting one. Not sure but its potentially possible. Its widely accepted (i think) that we do have antibodies to various animal tissue in our bodies as a result of medications and vaccines developed using animals. Doesn't get talked about much for some reason. I always thought it was quite remarkable!

Thanks, snowathlete!

snowathlete February 22, 2013 at 4:34 pm
anniekim

Is this suggesting that if the changes in the gut flora are corrected (I take it gut flora changes means too much bad bacteria?) this could bring benefit/resolve the subsequent immune problems? is this why some find correcting gut helpful? is it suggested that gut treatments are important?

Leachim shared above that 'De Meirleir's model of the disease process starts with disruptions in the gut flora causing an array of immune dysfunction'. Does KDM believe then if the gut is treated at the start of the illness the downstream processes can be stopped and these few patients if caught early enough can make good recoveries? I know of one young woman who hadn't been ill for long, saw kdm, followed his gut treatments and made a full recovery. Dont know whether it lasted. Know others ill longer, saw KDM, did his gut treatments with little to no benefit.

Yes bad bacteria, but also potentially other pathogens and toxins. There are other people on here with more experience of the gut than me. My own gut is generally good. It was bad at first then got better and the last month has been a little off again, but not as bad as before. I am waiting on test results though as I am told that your gut can be a mess even if you dont get lots of symptoms, so maybe mine is a mess. Dont know yet.
I think the paper is suggesting that the better state you can get your gut in so that it is functioning well and with the minimum of inflammation then the lower your expression of HERV proteins. HERVs aside, as you say, some people have had improvement by getting their gut right so worth trying in that area I think. Like you say though, some people still have problems even if they improve that area. I think as a general rule the longer your illness the worse your chances, but thats just my personal view. I may be wrong about that.
In the case of HERV expression, I dont know if fixing your gut would stop HERV expression altogether, and resolve the immune problem(s), but I think this paper, and other papers talking about HERVs, are saying that you should have less of a problem at least.
I'm going to be paying close attention to my gut test results and trying to improve there in any way I can.

Helene February 22, 2013 at 5:49 pm
anniekim

Helene, may I ask did you do the western blot igg and igm at Infectolab or the Ltt elispot, or perhaps both? I did the ltt elispot at infectolab which came out negative. Don't know whether should do the western blot too to be sure, just more money to pay out…

Yes, they are very very expensive. I suggest you write to them and ask just what you asked me. That is, can there still be a positive with the other tests.

I did the whole set for borrelia, as well as two other infections.

Helene February 22, 2013 at 5:53 pm
anniekim

Is this suggesting that if the changes in the gut flora are corrected (I take it gut flora changes means too much bad bacteria?) this could bring benefit/resolve the subsequent immune problems? is this why some find correcting gut helpful? is it suggested that gut treatments are important?

Leachim shared above that 'De Meirleir's model of the disease process starts with disruptions in the gut flora causing an array of immune dysfunction'. Does KDM believe then if the gut is treated at the start of the illness the downstream processes can be stopped and these few patients if caught early enough can make good recoveries? I know of one young woman who hadn't been ill for long, saw kdm, followed his gut treatments and made a full recovery. Dont know whether it lasted. Know others ill longer, saw KDM, did his gut treatments with little to no benefit.

But what does KDM give for the gut. Arabinogalactan. Daosin. And of course, antibiotics to kill of bad bacteria.

I have been interested in fecal transplants for this reason you all site regarding the gut. Dr. Broody in Australia has had some success with CFS using fecal transplants.

Two Canadian doctors have just invented synthetic feces for fecal transplants and this will be extraordinary. But it is. It widely available. And only to Canadians, and only for reclctrant cdifficile.

Fixing the gut is hard, I have found, and probiotics have not really lived up to expectations, at least the ones readily available.

caledonia February 22, 2013 at 7:45 pm

The question that comes to my mind is WHY – we all have HERVs, so why do some people react to them and not others. This is similar to EBV – most people have EBV, so why do some people have reactivations and not others. So this is just another symptom.

Also very small study, and still needs to be replicated.

Not impressed at this time. (Although well written article!)

Sushi February 22, 2013 at 7:49 pm
Helene

But what does KDM give for the gut. Arabinogalactan. Daosin. And of course, antibiotics to kill of bad bacteria….
Fixing the gut is hard, I have found, and probiotics have not really lived up to expectations, at least the ones readily available.

He also gives other things to individual patients depending on tests.

Best,
Sushi

alex3619 February 22, 2013 at 10:13 pm

http://wingsofhopefornid.blogspot.com.au/
This is a short interview with Lombardi on this paper.

Helen February 23, 2013 at 4:27 am

Caledonia:

The question that comes to my mind is WHY – we all have HERVs, so why do some people react to them and not others. This is similar to EBV – most people have EBV, so why do some people have reactivations and not others. So this is just another symptom.
Also very small study, and still needs to be replicated.
Not impressed at this time. (Although well written article!)
Hi Caledonia and all,
I do agree with you. Dr.Kenny de Meirleir was invited for a talk to the IAOMT group in Sweden. Researchers and doctors considered afterwards that he was more describing and treating symptoms, than the real cause of ME/CFS. Of course in IAOMT we are prone to blame most symptons on mercury poisoning- but as we think, this is of good reasons. Some PWME´s consulted KDM but had some weird experiences from that. No effect in the long run.
I recall that Rich (vank) told that he had seen more than 200 testresults from Vitamindiagnotics Methylation Panels sent to him from people with ME. All, except a few, showed a decreased methylation and low levels of glutathione. As we can see from the gene tests MTHFR and MTR/MTRR polymorphisms are very common in our group and these gene defects, or one of them, are sufficient to make people vulnerable for a partial methylation blockage.
It will be very interesting to see more of the results from 23and me. I would guess that many will have polymorphisms in the GST genes which means that they propbably can´t make use of their glutathione in a proper way. At least this is what I have seen when I have studied genetest results from Yasko´s Comprehensive Methylation Panel + Genovations genetest, that includes some GST genes, from a group in Sweden diagnosed with ME and mercury poisoning.
If we can´t make glutathione due to decreased methylation , and then can´t make use of the glutathione that we actually have in our bodies, then we can´t detox eg. mercury, mold, toxins from viruses and bacteria in a proper way.
Maybe this is a little of topic in this thread, but I just wanted to explain why we in the IAOMT group in Sweden are very sceptical to KDM´s hypothesis. It would be very interesting to get inputs from you on this.
Helen

anniekim February 23, 2013 at 4:56 am
snowathlete

Yes bad bacteria, but also potentially other pathogens and toxins. There are other people on here with more experience of the gut than me. My own gut is generally good. It was bad at first then got better and the last month has been a little off again, but not as bad as before. I am waiting on test results though as I am told that your gut can be a mess even if you dont get lots of symptoms, so maybe mine is a mess. Dont know yet.
I think the paper is suggesting that the better state you can get your gut in so that it is functioning well and with the minimum of inflammation then the lower your expression of HERV proteins. HERVs aside, as you say, some people have had improvement by getting their gut right so worth trying in that area I think. Like you say though, some people still have problems even if they improve that area. I think as a general rule the longer your illness the worse your chances, but thats just my personal view. I may be wrong about that.
In the case of HERV expression, I dont know if fixing your gut would stop HERV expression altogether, and resolve the immune problem(s), but I think this paper, and other papers talking about HERVs, are saying that you should have less of a problem at least.
I'm going to be paying close attention to my gut test results and trying to improve there in any way I can.

Thanks for answering my questions

anniekim February 23, 2013 at 5:00 am
Helene

Yes, they are very very expensive. I suggest you write to them and ask just what you asked me. That is, can there still be a positive with the other tests.

I did the whole set for borrelia, as well as two other infections.

Thanks Helene, will write to them, good suggestion. Did you test positive for both ltt elispot and western blot? Did you also test positive for the two co infections tested? I did cpn and bartonella and was negative for both of these. Many thanks

Helene February 23, 2013 at 8:01 am
anniekim

Thanks Helene, will write to them, good suggestion. Did you test positive for both ltt elispot and western blot? Did you also test positive for the two co infections tested? I did cpn and bartonella and was negative for both of these. Many thanks

dear Anniekim, alas, I did test positive for everything I sent in.

But I must be honest, and I have wonder if CFS is not an umbrella for a few comparable conditions, or conversely, is it that all these strange manifestations, borrelia, viral infections are all really one condition. I am having serious trouble with this.

Ps. I note we have another Helen in the thread, so I will just sign off Helene-Canada, don't want my babble mistaken for her lucid texts

Helene February 23, 2013 at 8:05 am
Helen
Hi Caledonia and all,
I do agree with you. Dr.Kenny de Meirleir was invited for a talk to the IAOMT group in Sweden. Researchers and doctors considered afterwards that he was more describing and treating symptoms, than the real cause of ME/CFS. Of course in IAOMT we are prone to blame most symptons on mercury poisoning- but as we think, this is of good reasons. Some PWME´s consulted KDM but had some weird experiences from that. No effect in the long run.
I recall that Rich (vank) told that he had seen more than 200 testresults from Vitamindiagnotics Methylation Panels sent to him from people with ME. All, except a few, showed a decreased methylation and low levels of glutathione. As we can see from the gene tests MTHFR and MTR/MTRR polymorphisms are very common in our group and these gene defects, or one of them, are sufficient to make people vulnerable for a partial methylation blockage.
It will be very interesting to see more of the results from 23and me. I would guess that many will have polymorphisms in the GST genes which means that they propbably can´t make use of their glutathione in a proper way. At least this is what I have seen when I have studied genetest results from Yasko´s Comprehensive Methylation Panel + Genovations genetest, that includes some GST genes, from a group in Sweden diagnosed with ME and mercury poisoning.
If we can´t make glutathione due to decreased methylation , and then can´t make use of the glutathione that we actually have in our bodies, then we can´t detox eg. mercury, mold, toxins from viruses and bacteria in a proper way.
Maybe this is a little of topic in this thread, but I just wanted to explain why we in the IAOMT group in Sweden are very sceptical to KDM´s hypothesis. It would be very interesting to get inputs from you on this.
Helen

Hello Helen,
What you say corresponds to what Rich van K told me after looking at lots of my tests. Glutathione not functioning properly. Rich sent me to KDM, in fact, to address the gut, however, this has not happened as yet.
Cannot eat without pain. Helene-canada

Helen February 23, 2013 at 9:07 am

Hi Helene-canada :),
My friends who tried treatment by KDM got even more trouble with their guts so they finished. One of them started on Rich´s protocol and is feeling good after one year of treatment – have been sick for 20. (She also removed her amalgam many years ago).

This study might be relevant in this thread:
Clinical activity of folinic acid in patients with chronic fatigue syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/?term=16889122

Joel, thank you very much for your article. I hope you don´t mind my doubts of the trial.

Lansbergen, it is interesting that some of the studies that you link to are about treatment of oral lichen. In Sweden you get free amalgam removal if you have oral lichen. It is stated, they mean, that oral lichen is caused by mercury in amalgam. Maybe they treated a symptom, not a cause in the trials.

In the IAOMT group in Sweden we wished that KDM had noted if his patients had amalgam fillings, or had before.

Helen- sweden

Helene February 23, 2013 at 9:55 am
Helen

Hi Helene-canada :),
My friends who tried treatment by KDM got even more trouble with their guts so they finished. One of them started on Rich´s protocol and is feeling good after one year of treatment – have been sick for 20. (She also removed her amalgam many years ago).

This study might be relevant in this thread:
Clinical activity of folinic acid in patients with chronic fatigue syndrome.

http://www.ncbi.nlm.nih.gov/pubmed/?term=16889122

Joel, thank you very much for your article. I hope you don´t mind my doubts of the trial.

Lansbergen, it is interesting that some of the studies that you link to are about treatment of oral lichen. In Sweden you get free amalgam removal if you have oral lichen. It is stated, they mean, that oral lichen is caused by mercury in amalgam. Maybe they treated a symptom, not a cause in the trials.

In the IAOMT group in Sweden we wished that KDM had noted if his patients had amalgam fillings, or had before.

Helen- sweden

Hello again,
Yes, dear Rich suggested Folinic acid, and I did as he said, with this and Vit b12, but nothing seemed to alter . The dose is not specified there.

I miss Rich very much. He was always willing to adjust things, to help, such a decent man…I just don't know where to turn with him gone.

The other point I wish to make is that for a decade now, I have gone to a variety of CFS specialists,borrelia specialists, and the cardinal problem is that they give a protocol, and then one just goes home and has to try it. The doctor is far, overseas, across the continent. This results in telephone medicine. Ok, so I tried to park myself near the doctor, but that did,not change because he is usually busy sees you for a few minutes, and agin, off you go with try this.

Some folks aren't that sick, and this works, but for delicate constitutions and very sick people there should be a clinic like setting where one is helped and monitored every day for several months.

I looked at evita, but they have no MD doctors there, only naturopaths. The closest I see is Augsburg, but,you do not sleep there.

anniekim February 23, 2013 at 10:59 am
snowathlete

Yes bad bacteria, but also potentially other pathogens and toxins. There are other people on here with more experience of the gut than me. My own gut is generally good. It was bad at first then got better and the last month has been a little off again, but not as bad as before. I am waiting on test results though as I am told that your gut can be a mess even if you dont get lots of symptoms, so maybe mine is a mess. Dont know yet.
I think the paper is suggesting that the better state you can get your gut in so that it is functioning well and with the minimum of inflammation then the lower your expression of HERV proteins. HERVs aside, as you say, some people have had improvement by getting their gut right so worth trying in that area I think. Like you say though, some people still have problems even if they improve that area. I think as a general rule the longer your illness the worse your chances, but thats just my personal view. I may be wrong about that.
In the case of HERV expression, I dont know if fixing your gut would stop HERV expression altogether, and resolve the immune problem(s), but I think this paper, and other papers talking about HERVs, are saying that you should have less of a problem at least.
I'm going to be paying close attention to my gut test results and trying to improve there in any way I can.

Snowathlete, may I ask which gut tests you have recently done? Perhaps cdsa, sibo, leaky gut? Many thanks

snowathlete February 23, 2013 at 12:03 pm
Helen

Joel, thank you very much for your article. I hope you don´t mind my doubts of the trial.
Helen- sweden

Not at all Helen. I welcome a healthy discussion and sharing of views!

anniekim

Snowathlete, may I ask which gut tests you have recently done? Perhaps cdsa, sibo, leaky gut? Many thanks

I've had the stool test to look for bacteria etc, the redlebs one. Also soluble CD14. I understand this is an indicator of leaky gut. I think it's related to lipopolysaccharide (LPS) in your blood, that can get through your leaky gut, but i dont know much more than that yet.

HowToEscape? February 23, 2013 at 12:24 pm
Helene
anniekim

Thanks Helene, will write to them, good suggestion. Did you test positive for both ltt elispot and western blot? Did you also test positive for the two co infections tested? I did cpn and bartonella and was negative for both of these. Many thanks

dear Anniekim, alas, I did test positive for everything I sent in.

But I must be honest, and I have wonder if CFS is not an umbrella for a few comparable conditions, or conversely, is it that all these strange manifestations, borrelia, viral infections are all really one condition. I am having serious trouble with this.

Ps. I note we have another Helen in the thread, so I will just sign off Helene-Canada, don't want my babble mistaken for her lucid texts

" if CFS is not an umbrella for a few comparable conditions"

Most likely so. We have a condition with multiple, somewhat vague definitions each of which circumscribe a wide variety of symptoms. Some of these are specific, such as getting vertigo after acceleration (being passenger in traffic), becoming suddenly knocked out a certain time after exposure to normal heat (hot shower, normal hot outdoor temps), while others, at least in words, describe effects of any debilitating chronic disease.

Fatigue in particular is a misleading term; I've done 180 mile bike rides through hilly country and had nothing like the wipeout delivered by CF/ME/whateveryacallit. It's a sensation more like one's blood draining out.

A more specific list of symptoms may correlate to a specific underlying disease, and we may find several symptom patters which _may_ link to different diseases. We could also be in different stages or manifestations of a common disease.
But right now we only know the effects and have a feel for the causes.

This is definitely a condition of no interest to the lazy of mind. They don't "get it" and never will.

Daffodil February 23, 2013 at 7:10 pm

you know whats interesting…a couple of months after i got sick, i started having weird gut reactions to food….and also i would go through phases of diarrhea and constipation ..i knew there was something wrong in there but didnt know what. i would wake up with the WORSE imagineable nausea for months. these episodes went on for years.

eventually, the old gut symptoms stopped. but then, i started having HORRIBLE flatulence. and these weren't just any farts……they were so intense and horrid, that my own family would not want to sit beside me anymore. my own mother got up from a bus seat beside me once and changed places!! again, i knew there was something very very wrong inside me but didnt know what.

that went on for several months..maybe a year or 2…i cannot remember….and then it all stopped. now..i KNEW that didn't mean i was better, cuz my CFS was very bad….i kind of felt like, the gut reactions i was having was sort of a good thing – like my body was trying to do something – but it had lost and given up. it couldnt kill the bad bacteria anymore, hence maybe the gases had stopped(?)

then, another strange thing started to happen….my whole back and shoulders started to get cystic acne! this went on for a couple of years..i even went to dermatologists and used topical creams because I could not even sleep sometimes from the painful pustules! i think i still have some scarring.

again, my CFS was getting worse and worse and I knew something very insidious was going on. it was as if the bacteria was going from my gut, right into my bloodstream! my gut could no longer stop it!

5150 February 24, 2013 at 1:35 am
lansbergen
5150

Re "autoimmune" : how does the very obvious fact(in my cohort anyway) that CFS/ME is Contagious , fit into the HERV implicated theory? I was fine until I was exposed to someone else's really powerful and bad HERV? Because I was just great until that event, after which my life went to hell. So there's an extremely virile contagious HERV out there? and where did it come from? indigenous somewhere? or what. Thanks.

HERVs can be activated by another infection.

this is certainly what happened to me. got a pretty bad "cold", after which i was lactose intolerant. lost my immune system right there. And, as the old saying goes, it was all downhill from there. one thing progressing to the next. will be checking for lymphoma soon, actually asap.

free at last February 24, 2013 at 3:02 am

Hi Everyone. Not sure what to make of this paper. Other than to say it certainly seems relevent to me presently. Ive always had gut problems. recently had two ( just outside of the colon ) abcesses, and will be haveing a crohns test. I am also suffering from and being tested for bone problems ( possibly inflamation) in my shoulders knees and feet. and recently suspected stomach ulcer. over production of stomach acid. Body aching i would certainly suggest is autoimmune, as might be bowel and stomach problems that i have always had. And are now getting far worse. I will keep everyone updated on the crohns test and the bone investigations. Interesting paper. Autoimmune is a word ive been reading a lot lately with my present problems Hmmm

Enid February 24, 2013 at 8:27 am

Wow – thanks Joel – this explains so much – and thanks to KDM for his sheer hard work and persistance.

David Egan February 24, 2013 at 10:15 am

This confirms other studies. The HERV study results from Tufts University are due this year. The current scientific understanding is that certain viruses such as EBV and herpes viruses 1-9 re-activate HERV viruses which are inherited and part of human DNA. These HERV viruses contain super-antigens which cause havoc for the immune system. This leads to chronic activation of the immune system and higher usage of ATP and to total exhaustion of the body.
HERV's are also implicated in AIDS and MS, but they are not the root causes. HERV is a secondary effect of some other attack such as Herpes viruses 1-9 or some other virus which acts as the trigger mechanism.

alex3619 February 24, 2013 at 11:02 am

On superantigens and autoimmune disease:

"Autoimmune diseases

It has been proposed that SAgs might contribute to the pathogenesis of autoimmune disease by activating T cells that are specific for self antigens. Although there is no direct evidence of SAg involvement, it has been suggested that SAgs could, under the right conditions, break the tolerance or suppression of auto-reactive T cell clones and induce a state of autoimmunity. Evidence for this hypothesis came from an animal model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE), where it was shown that administration of SEB to mice recovering from EAE triggered direct stimulation of the Vβ3 positive auto-reactive MBP peptide specific T cells resulting in a rapid relapse of the disease [73,74].
Conrad and colleagues found a biased TcR usage in T cells from IDMM patients towards Vβ7 suggesting the activity of a SAg [58]. They showed that the mitogenic activity was encoded by a gene residing on an endogenous retrovirus, named IDDMK1,222 and that viral expression occurred only in IDMM patients. It was shown later by the same group that IDDMK1,222 is identical to one allele of the EBV-inducible HERV-K18 carrying the Vβ7-specific SAg K18·3 [56] (see above)." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808794/
[my bolding]

I would like to point out though that if we have LPS in the blood, and we have any of the bacteria or viruses that produce superantigens, then superantigens will likely get into our general circulation as well – LPS is a marker of detox failure in my opinion. Staph aureus is the classic superantigen producer, but it is far from alone. Various staph and strep bacteria produce these. Its also worth noting that we tend to have chronic staph or strep nasal infections. Even mycobacteria make them. EBV is thought to have a superantigen.

I am interested in gamma delta T cells due to their super sensitivity to bacterial toxins/markers and their function in suppressing excess immune stimulation. They activate or deactivate the immune system, talk to dendritic cells, and accelerate wound healing.

Old Salt February 24, 2013 at 4:22 pm

It would seem, most of the degenerative diseases would originate and emanate from the gut, as that is where most of the things enter our body, good and bad. It would also explain why the immune system also evolved mostly in the gut, to deal with this stuff. We should know much more than we do!

Daffodil February 24, 2013 at 8:03 pm

i agree. no wonder the small and large intestines are supposed to be as big as a football field, if combined and unfolded….and it has been largely ignored all this time! the brain is full of folds too and we hardly know anything about that either…..the gut is like a second brain, they say now.

my doc says "whats there to know? there is bacteria…it digests your food, your nutrients are absorbed, thats about it" WTF!!!

serg1942 February 25, 2013 at 12:26 pm

Hi to everybody,

I first studied the paper and throw several questions, that I have yet to discuss with some of you to try to solve them. I will also consult with some experts on the subject. Anyhow, and after having "dissected" again the study, I have actually realized that my doubts are actually beyond what it's explained in the paper, in an effort to put together these pieces in order to understand how all this could actually lead to an autoimmune process and finally to the symptoms of CFS.

I have written an article quite similar to that of Joel, in Spanish. I am posting it here for what it may be worth:

http://www.sfc-em-investigacion.com/download/file.php?id=238

There's no need to translate this into English, thanks to the fantastic job Joel and others are doing. However, I enjoyed preparing this drawing in English, and I thought I would share it with you. Maybe some of you can help me out with the interrogation marks I have placed in the sketch, and of course, probably some of you will correct it… It can be funny! ;)

http://www.sfc-em-investigacion.com/download/file.php?id=237&mode=view

Sergio

jimells February 25, 2013 at 12:45 pm
Daffodil

my doc says "whats there to know? there is bacteria…it digests your food, your nutrients are absorbed, thats about it" WTF!!!

Must be nice to know all there is to know about a subject! I'll bet this doctor "knows" that if a ship gets too close to the edge of the Earth, it will fall off, and that the Sun revolves around the Earth, LOL

snowathlete February 25, 2013 at 6:02 pm
serg1942

Hi to everybody,

I first studied the paper and throw several questions, that I have yet to discuss with some of you to try to solve them. I will also consult with some experts on the subject. Anyhow, and after having "dissected" again the study, I have actually realized that my doubts are actually beyond what it's explained in the paper, in an effort to put together these pieces in order to understand how all this could actually lead to an autoimmune process and finally to the symptoms of CFS.

I have written an article quite similar to that of Joel, in Spanish. I am posting it here for what it may be worth:

http://www.sfc-em-investigacion.com/download/file.php?id=238

There's no need to translate this into English, thanks to the fantastic job Joel and others are doing. However, I enjoyed preparing this drawing in English, and I thought I would share it with you. Maybe some of you can help me out with the interrogation marks I have placed in the sketch, and of course, probably some of you will correct it… It can be funny! ;)

http://www.sfc-em-investigacion.com/download/file.php?id=237&mode=view

Sergio

Hi Sergio,

Great work putting something together in Spanish! Nice diagram too! I sent you a PM about this, but in case anyone else in interested, I thought I'd post something general about it here too.

As you've probably seen the paper makes reference to 'unpublished data' a couple of times, so I expect there is more information to come. Also the WPI haven't yet published the video of De Meirleir's recent talk, titled "ME/CFS: from Infectious Disease to Autoimmune Disorder". I think they will post it on their blog once the other paper is published. That no doubt will give us some of the details we crave!

However, they have already published a general summary on their blog, in which they mention Th17 cells which are immune cells linked to several other autoimmune conditions, MS, RA, Crohns, etc.

The blog also mentions aberrant protein conformation which I'm not that clued up on yet, but in short: proteins expressed by cells do various tasks and to do those tasks each proteins forms a specific structure. but proteins can sometimes form an incorrect structure and when that happens the protein may have modified functionality. I guess there is room for this to be part of the cause of autoimmunity, but I’m just guessing on that.

If it is autoimmune then it is likely that B cells are affected and I think it is interesting that the Mella and Fluge study using Rituximab reported improvement in about the same proportion of patients as were found to have HERV proteins in this study from De Meirleir and Lombardi.

ME shares many characteristics with known autoimmune diseases, such as a higher occurrence in females than men, improved symptoms during pregnancy, immune dysfunction, family history of autoimmunity etc. Add to that the link with pathogens such as EBV that are thought to play a role in autoimmunity, and now HERVs being found in major antigen-presenting cells…

For me, the increased number of women with ME compared to men is the most striking link. I think it is most likely down to genetics, specifically the X chromosome but it's not out of the question that it is hormonal, or a bit of both.
This new study on MS talks about an increased DNA copy number of HERV-W in MS. Which is strongly linked with the pathopysiology of MS via the MSRV.
http://www.ncbi.nlm.nih.gov/pubmed/23308264

Here is another paper on MS looking at MS-implicated HERVs on the x chromosome.
http://www.retrovirology.com/content/8/S2/P54

Even the most commonly accepted cause of autoimmunity, via molecular mimicry is often complex so I don't imagine De Meirleir, Lombardi et al have the whole picture yet, and even acknowledged autoimmune diseases are not understood that well yet. Still, that needn't stop us thinking about it and discussing the possibilities. I don't know if anyone would be interested in an article looking at autoimmunity in general, or not, but if there is enough interest then maybe I'll put something together…

Best
Joel

lansbergen February 25, 2013 at 6:12 pm

The blog also mentions aberrant protein conformation

KDM is talking about that for years and in the presentation in dutch I saw it is mentioned by name.

Sushi February 25, 2013 at 6:53 pm
lansbergen

KDM is talking about that for years and in the presentation in dutch I saw it is mentioned by name.

The test is PrPc functional testing–mis-folded cell surface proteins. I have had it.

Sushi

Legolas February 27, 2013 at 4:16 pm

I've put below a link of an article about a specific HERV and MS, some lines from the article and an image expressing the general hypothesis.
Since MS is kind of put forward as a possible model for ME, this could be relevant.
Anyway, i think it's interesting.

http://msj.sagepub.com/content/18/12/1721.full.pdf html

These results together with the many others
accumulated over the past two decades indicate that this
MSRV subtype of the HERV-W family is likely to play a role
in initiating and fueling a pathogenic ’chain reaction’ causing
MS.
Based on the present observations and on the preclinical
efficacy of an anti-Env neutralizing monoclonal antibody
in MS-like EAE animal models induced by HERV-W Env,
as evoked above in this discussion, a humanized antibody is
now to be evaluated in clinical trials with MS patients
(Clinical Phase I has been achieved).
[​IMG]

lansbergen February 27, 2013 at 5:34 pm
Sushi

The test is PrPc functional testing–mis-folded cell surface proteins. I have had it.

Sushi

The patent http://www.freshpatents.com/-dt20120119ptan20120015390.php

girlinthesnow February 28, 2013 at 7:14 am
alex3619

On superantigens and autoimmune disease:

"Autoimmune diseases

It has been proposed that SAgs might contribute to the pathogenesis of autoimmune disease by activating T cells that are specific for self antigens. Although there is no direct evidence of SAg involvement, it has been suggested that SAgs could, under the right conditions, break the tolerance or suppression of auto-reactive T cell clones and induce a state of autoimmunity. Evidence for this hypothesis came from an animal model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE), where it was shown that administration of SEB to mice recovering from EAE triggered direct stimulation of the Vβ3 positive auto-reactive MBP peptide specific T cells resulting in a rapid relapse of the disease [73,74].
Conrad and colleagues found a biased TcR usage in T cells from IDMM patients towards Vβ7 suggesting the activity of a SAg [58]. They showed that the mitogenic activity was encoded by a gene residing on an endogenous retrovirus, named IDDMK1,222 and that viral expression occurred only in IDMM patients. It was shown later by the same group that IDDMK1,222 is identical to one allele of the EBV-inducible HERV-K18 carrying the Vβ7-specific SAg K18·3 [56] (see above)." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808794/
[my bolding]

I would like to point out though that if we have LPS in the blood, and we have any of the bacteria or viruses that produce superantigens, then superantigens will likely get into our general circulation as well – LPS is a marker of detox failure in my opinion. Staph aureus is the classic superantigen producer, but it is far from alone. Various staph and strep bacteria produce these. Its also worth noting that we tend to have chronic staph or strep nasal infections. Even mycobacteria make them. EBV is thought to have a superantigen.

I am interested in gamma delta T cells due to their super sensitivity to bacterial toxins/markers and their function in suppressing excess immune stimulation. They activate or deactivate the immune system, talk to dendritic cells, and accelerate wound healing.

Very interesting post Alex, my IL17 is sky high ( as is my CD14s), so the gamma delta T cells and autoimmunity connection looks like a potent area for research for those pwME whose disease is gut based.

Enid March 18, 2013 at 8:04 am

Thanks snowathlete – stunning news and very welcome progress from KDM and his team.

Enid March 18, 2013 at 8:15 am

Can I add – on the gender bias it does not seem to be so in my case. I (UK) went down first and brother (US) went down a year later. His even more severe than my own severities apparently exhibiting more dangerous latent viruses such as JCV (think that's the one – affects the brain).

snowathlete March 19, 2013 at 7:24 pm
Enid

Can I add – on the gender bias it does not seem to be so in my case. I (UK) went down first and brother (US) went down a year later. His even more severe than my own severities apparently exhibiting more dangerous latent viruses such as JCV (think that's the one – affects the brain).

Interesting, JCV infects the GI tract as well as the brain. I think i read/heard somewhere about autoimmune conditions presenting more severely in the men that do get them too.

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