Lipkin Study Press Conference 18th Sept

[Mark]

I don't really know why, as I know nothing about this area, but I feel instinctively sceptical when I hear people talk about immune abnormalities in CFS.

Esther, if you don't know anything about the immune abnormalities in ME, I really, really think you should challenge your scepticism and learn up on the subject by reviewing this article, starting on page 32.
http://www.mecfs-vic.org.au/sites/w...0of%20IiME%20Vol%206%20Issue%201%20Screen.pdf

I defy anyone to actually read through that history of scientific results going all the way back to 1983, and still doubt that there is ample evidence of immune abnormalities in ME/CFS. It might be best to start with the most recent research, going backwards from page 95. Yes, a 63-page summary of 30 years of scientific evidence of immune abnormalities in ME is a bit much to wade through. I'm not suggesting you read every word, but as you scan through it you should see that, although there are complexities and contradictions as the science evolves historically, there's also a fairly clear and evolving picture of the science as well, with multiple researchers over decades refining the same findings: impaired natural killer cell function, abnormal levels of lymphocytes, particularly during and after exercise, and multiple lines of evidence for chronic immune activation.

There is just too much of this evidence, from too many respected researchers, for it to be dismissed. Indeed, that's why the MRC recently acknowledged this evidence in their call for research. If you're sceptical about Margaret Williams, what do you think about this statement, from the MRC?

Immune dysregulation: There is evidence for a disturbance in innate and adaptive immunity in CFS/ME including alterations in cytokine profile, absolute and functional alterations in T cells and NK cells and occurrence of autoantibodies and allergic reactions that may explain some of the manifestations such as fatigue and flu-like symptoms. A number of infectious and environmental exposures have been associated as triggering these changes.
http://www.mrc.ac.uk/Fundingopportunities/Calls/MechanismsofCFSME/MRC007715

Anyway, for myself, I've had batteries of blood tests over my 17+ years of illness, and the only NHS one that has showed consistent abnormalities is the white blood cell count I had done 4 times last year, every time well above the reference range. That suggests persistent infection, or at least persistent immune activation. I only got that test done because I asked for it specifically based on precise information from this forum. So however sceptical I may be, I can at the very least say that there are definitely documented immune abnormalities in me...and if you're still sceptical I suggest you pursue similar tests yourself.

 

[alex3619]

Here we are nearly 30 years after the epidemics that gave rise to "CFS" and we are no further forward to explaining them.

I don't think we are going to get a better study than the mBio one for XMRV and CFS, it will be hard to justify cost. However, I also don't think the epidemics have stopped. I think they have been relabelled. So we have post-Q fever, and post SARS syndromes, not ME. They now label them with the pathogen they find epidemic at the location. I hope to write a blog on this some seven or eight blogs from now.

Bye, Alex

 

[ukxmrv]

Alex, a better study for XMRV and CFS (and for Retroviruses and ME) could be one maybe include epidemic patients like the recent Hanson paper

I'm reading through the Lipkin paper still but listened to the TWIV and the press release

What is missing maybe are the epidemic patients. There is no mention that I can see of these

We don't have any proof that post-SARS, post Q-fever etc is the same as ME

 

[SOC]

However, I also don't think the epidemics have stopped.

I was talking to a friend today about the unusual number of ME/CFS, Fibromyalgia, Lyme, MS and "unknown" diagnoses there are in our homeschool group. She said that it's even worse in her church.

The patients are young people between about 17 and 24yo, their mothers, and a few fathers. As we discussed this, we thought about an outbreak of Fifth Disease (HHV-6) we had 15 years ago. The afflicted kids would have been about 2 to 10 years old -- just the age of the kids in the homeschool playgroup.

My friend said this summer one of the families in her church had Fifth Disease as teens and adults (quite unusual). We are wondering if we had an outbreak of HHV-6A (not the more common HHV-6B) in this area and are continuing to circulate it to a lesser degree. Doctors know nothing about HHV-6A and don't test for HHV-6 at all, so they could easily be missing an outbreak.

Whether or not it's the HHV-6, it's clear there's something really going wrong in these families connected by either homeschooling or church. But no doctor has noticed. Maybe part of the reason is that they are giving multiple diagnoses to similar symptoms.

The point of all that babble is that I don't think the epidemics have stopped, they're just not being recognized (or acknowledged).

 

[rlc]

Hi Mark, sorry going slightly of topic, RE your high white blood cell count, yes it can be a sign of infection or immune activation but it is also found in many other diseases such as Addison’s and leukemia, 365 diseases are listed as causing high white blood cell count see http://en.diagnosispro.com/differential_diagnosis-for/infected-organ-abscesses-wbc-white-blood-cell-count-leukocytes-lab-increased/10100-154-90.html white blood cell count is one of the tests that nobody with CFS or ME is supposed to fail because they are not supposed to fail these kinds of common tests, High white blood cell counts was also never found in any of the ME epidemics. This kind of failed tests result should lead to an extensive investigation to find the cause of it, because many of the diseases that can cause it will ultimately be fatal. So I would recommend that you don’t see it as confirmation of immune activation in ME but as a sign to tell your doctor to get there a into g and start looking for the cause. There is more information on this test here http://labtestsonline.org/understanding/analytes/wbc/tab/test

Sorry to go of topic but failing that tests can be very serious and is highly unlikely that your results are caused by ME.

Hope this helps

All the best

 

[beaverfury]

Re: Lipkin talking about advocacy pressure, publicity and making a loud noise.

LETS DO AN OLD STYLE AMERICAN POSSE and post a $1 000 000 REWARD for the scientist that cracks the code
Ridiculously Hollywood and scientifically ineffectual- but PUBLICITY!!! I can donate $5

...I mean, look how quickly they tracked down Osama Bin Laden!

 

[alex3619]

On the flip side of white white blood cell counts, we have a tendency to leukemia and lymphoma. Nobody knows what the precursor stage is. So at some point many ME patients are likely to have a high white cell count, even without leukemia or lymphoma. It needs to be monitored. This would not show up in epidemics as its a long term consequence in subsets of patients. The high white cell count might be a stage that indicates increased risk of leukemia or lymphoma. I wish I knew more, but most of the science is vague. There are other such risk factors. One I have had is a hemangioma. Bye, Alex

 

[alex3619]

Alex, a better study for XMRV and CFS (and for Retroviruses and ME) could be one maybe include epidemic patients like the recent Hanson paper

I'm reading through the Lipkin paper still but listened to the TWIV and the press release

What is missing maybe are the epidemic patients. There is no mention that I can see of these

We don't have any proof that post-SARS, post Q-fever etc is the same as ME

Hi ukxmrv, we do not have any proof that postSARS or postQ or postPolio are the same as ME. Similarly we do not have any proof they are not. ME epidemics closely followed polio and coxsackie epidemics historically. If, as many are starting to think, ME is an immune consequence of certain pathogens in a subset of patients, the pathogen is not very relevant to causation, its just a trigger. It might be relevant to treatment if its persistent. The list of pathogens associated with ME is very long - its highly likely that many of them trigger ME in my opinion. That is they are part of a causal sequence involving genetics, nutrition and co-morbid conditions that initiates ME, but not terrible relevant once ME is present. Q-fever is one pathogen suspected of initiating ME. The question has also been asked about SARS but no conclusion has been drawn that I see.

In Scandinavia many with post-Q are diagnosed with ME long after the epidemic has been written off as post-Q fever. I hope to detail this at some point, but maybe some of our members from these countries can comment.

Bye, Alex

 

[currer]

I am dubious about pathogens as such causing this disease. I think we have to search for another reason as to why the immune system reacts abnormally in the first place.

I still think ASIA syndrome a good place to start looking, but I doubt this will happen.
http://www.ncbi.nlm.nih.gov/pubmed/20708902

I was concerned by the linking of the debunking of XMRV with the debunking of MMR and autism.in the nature article.
I suppose I am suspicious by nature.....but it smacks of propaganda.
http://www.nature.com/news/the-scientist-who-put-the-nail-in-xmrv-s-coffin-1.11444

 

[Simon]

re psychosomatic: Ah... okay. I haven't seen the video, and know that people can see 'psychosomatic' as synonymous with 'not real', so thought that he may have been using 'psychosomatic' in that lay manner.

No, I don't think he was, but was talking about sick specifically in the sense of an abnormal immune system, I don't think he was in anyway implying that psychosomatic was not real or not an illness, but saying why CFS wasn;t psychosomatic. But i think that's clearer when you see the video (@25mins ish).

I don't really know why, as I know nothing about this area, but I feel instinctively sceptical when I hear people talk about immune abnormalities in CFS. I think I'm sceptical of any claim at all about CFS at this point, perhaps because I tend to read Oxford criteria psychological papers. I should probably try to find the time to look more seriously at the evidence around CFS and immune abnormalities. (Actually, that doesn't sound super fun).

I share some of the scepticism. Of all the specific claims, only reduced NK cell activity looks robust (on average, with much overlap between patients and controls). However, if you look at the field as a whole, i would say there is evidence of a disturbed immune system. The immune system is incredibly hard to pin down as studies of cytokines in other fields shows: it will take a really good study to get a handle on what exactly is going on (and what is specific to CFS). Hopefully new studies on the new and very well defined cohorts will do that.

 

[Seven7]

On the flip side of white white blood cell counts, we have a tendency to leukemia and lymphoma. Nobody knows what the precursor stage is. So at some point many ME patients are likely to have a high white cell count Bye, Alex

The Doctor Run 2 sets of test, white blood cell like regular Doctors run which was normal and the other which is the deeper white cell count and that was abnormal. She showed my why the normal doctor find all ok. I think is all about ratio, So she told me that one arm was high the other arm was low so when you did the ratio, Mine was normal (or something like that sorry had brain fog) but the point is that your immune system can compensate showing normal blood count, like in my case, and you still have issues. So be careful to dismiss because the regular test is ok. I made that mistake.

 

[Seven7]

For those skeptical on abnormalities on Immune system: the tests I had: NK cell Number and activity (activity is less available). Lymphocyte subpanel, cytikones. Plus all the Viral Igms and Iggs.

You can have a skype consultation ($US175 or so???) maybe w Elander or one of those that have that service and asks for the tests. I know a few people that have been allowed to send the blood as a kit (Has to be there in less than 24h for NK) because they were too sick to go to consultation (and save all that travel money).

This has done the world difference to me, My GP and all others Drs say Ok I know something is wrong now that we have this tests, "I don't know what is wrong" they say, but they are more open to try stuff and my support from family and Drs has made it all worth it!!!

 

[beaverfury]

Just curious. I dont have a television. Did any of this rate a mention in mainstream media in any country?

Horribly naive, i know. I realize this issue doesnt and cant relate to 99% of the populous. I need to freakin get out more!
Get a hobby, get a life, get a wife, get a job, get a . . salamander! GET OFF phoenix rising!!
Make an appointment with Wesseley to discuss secondary gains and childhood issues

 

[Sasha]

Just curious. I dont have a television. Did any of this rate a mention in mainstream media in any country?

Horribly naive, i know. I realize this issue doesnt and cant relate to 99% of the populous. I need to freakin get out more!
Get a hobby, get a life, get a wife, get a job, get a . . salamander! GET OFF phoenix rising!!
Make an appointment with Wesseley to discuss secondary gains and childhood issues

I haven't noticed anything here on UK TV or radio but haven't been watching much - positive results tend to get more coverage than non-confirmations, I suppose. There was a lot of coverage of the original XMRV finding in October 2010.

Maybe we should all get salamanders!

 

[Enid]

More cautious now - the press - too much science and expertise confounding ?. How sad for the press when sound bites unfailingly miss real content by the experts - Lipkin et al.

 

[richvank]

Hi, all.

With regard to the discussion here about immune abnormalities in ME/CFS, what I would like to see is a study that looked for the most common inherited immune deficiencies in PWMEs. I think it is well established that there is immune dysfunction after a person has developed ME/CFS, but what I would like to see focus on is genetic abnormalities involving the immune system that people start out with.

I think there has to be a reason why about 90% of people who get mononucleosis, Q fever, or Ross River virus (as in the Dubbo study in Australia) are able to recover, while about 10% stay chronically ill. And also, there has to be a reason why this 10% had more severe illness during the chronic phase. I suspect that these people started out with genetic abnormalities in their immune system, which prevented it from being able to ward off the chronic disease.

There are many known inherited immunodeficiencies. I don't think very many PWMEs have been tested for them; and I think it would be instructive to do this. I have heard from a few who were found to have IgG subclass deficiencies, including IgG subclasses 1 or 3. I also heard from one person who was found to have mannose binding lectin deficiency. It is known that these deficiencies will make people susceptible to infections, and some of these people have been fighting infections since an early age. Some have had tonsillectomies at early ages because of persistent throat infections.

As many of you know, I am the proponent of the Glutathione Depletion--Methylation Cycle Block hypothesis for the pathogenesis and pathophysiology of ME/CFS. As far as I can tell, this hypothesis is continuing to hold up as more research is being done, given that I have had to make a few changes and additions to it over time as more has been learned about ME/CFS. I think it is becoming increasingly likely that the "trip wire" for developing ME/CFS in most cases is the depletion of glutathione. If this is true, then the genetic factors that will matter are those that either inhibit the ability to make or recycle glutathione, or those that foster ongoing oxidative stress, which tends to deplete glutathione. In autism, which shares a lot of its biochemical abnormality with ME/CFS, certain genetic polymorphisms in the glutathione system have been found to increase the risk of developing autism by a factor of 4 (400%).

One of main depletors of glutathione is inflammation, which is produced by the immune system in response to infections. If there is an inherited immune deficiency that prevents successful elimination of the infection in the usual amount of time, the inflammation will persist, and over time I think that the accompanying oxidative stress will tend to deplete glutathione. This would be especially true if the person also had certain polymorphisms in enzymes affecting glutathione synthesis or recycling.

So I think that looking for inherited immune deficiencies would help us to understand why some people get ME/CFS, while most others, subjected to the same infectious diseases, do not.

While knowing this might not lead directly to treatments, I think we have to find out the basic causes of ME/CFS before we can know how to try to treat it.

I would appreciate comments on this, and especially would like to know if any of you have had any inherited immune deficiencies identified, or if you have had infections more or less continuously since an early age, or if you had a tonsillectomy at an early age.

Thanks.

Best regards,

Rich

 

[Simon]

Lipkin: This is not a psychosomatic disorder

I'm going through the video at the moment. I could watch Lipkin all day, the man is a class act both as a scientist and as an all-round smart operator. Better stop gushing now.

This struck me as interesting, @ 25' in the Press Conference video. Apologies if it has been posted already.

Commenting about his first foray into CFS research, he talked about a Japanese studies in the 1990s that said 50% of CFS cases in Japan were due to Borna Disease Virus (which Lipkin co-discovered). Lipkin and co. looked but couldn't find any link between CFS and the virus, but at today's press conference he said about that work:

Thought people might like to read the extra detail Ian Lipkin gave to Vincent Racaniello in the latest TwiV:

transcript for mecfsforums Wiki - worked on by Wildaisy, and others. thanks!

Many, many years ago when I was working with…I was asked by CDC to look into the potential role of Borna Virus and Chronic Fatigue Syndrome … this was back in the mid 1990’s to late 1990’s, there was a report that came out of Japan suggesting that Borna Virus was implicated. And 50 percent of cases were reported to have nucleic acids and there was a family found where three-quarters of the people in the family had Borna Virus nucleic acids, and were also antibody positive. So Brian Mahy, who was then Director of DVRDD, who ran afoul, ad you may remember, of this whole issue of whether or not enough money was being invested in this research, asked me to look into this, and I looked into Gulf War Syndrome which was also very topical at the time and I looked at these Chronic Fatigue Syndrome patients, many of them coming out of a clinic that was run in the Karolinska, which at that point was one of the best clinics for CFS in the world. And we found no evidence of Borna Virus nucleic acids. And our ELISA’s were positive but our Western Blots were negative.


And when I tried to report this finding, I wound up going to progressively less impressive journals until I finally wound up with the one in which it was published. And there was a great deal of reluctance to publish the paper because, the saying at that point was, you know, you’re just not good enough at doing this, and this was why it’s all negative.

(Racaniello laughs.)

And it took almost two years to publish that particular paper, which is how I learned the lesson of making certain that people who originally do the report are the ones who are engaged in proving or disproving the concept.

But at that point, the one thing that struck me was that many of these individuals, I think it was close to two-thirds, something like 67 percent, were reactive with Borna Virus proteins in ELISA but negative in Western Blot, but they were also reactive with FLG (?) and Beta galactacytase, and I would love to conclude that they had polyclonal B-cell activation, so at the very end of this paper which appears in the Journal of Neurovirology, I said these patients are clearly sick in some way. They have some kind of immunological activation. I don’t know why, but it is not Borna Virus.

So I am convinced, after working in this field for, you know, for a very long time, that this is a bona fide syndrome. I don’t believe that it necessarily has a single cause. I don’t pretend to have insights into the pathogenesis of CFS, but one of the things that we want the community to take away very clearly is that the people who have engaged in this study and many others around the world are committed to trying to understand why they’re ill. We have reagents , we have resources now that can be applied to this task, and that just because this particular hypothesis hasn’t borne fruit does not mean that there won’t be an answer downstream. And we’re trying, you know, to do that work as rapidly and efficiently and as rigorously as we can.

Here, Lipkin doesn't even refer to psychosomatic, but I suppost you could take his reference to 'bona-fide' syndrome as meaning psychosomatic syndromes are not real - but his background is in infectious diseases and I think he just mean there is something abnormal with the immune system that suggests a biological cause.

 

[urbantravels]

"Bona fide" syndrome could also mean that ME/CFS is not just a "wastebasket" of people with unexplained fatigue, but a disease with consistent manifestations of immune dysfunction among properly characterized patients.

 

[WillowJ]

I would appreciate comments on this, and especially would like to know if any of you have had any inherited immune deficiencies identified, or if you have had infections more or less continuously since an early age, or if you had a tonsillectomy at an early age.

hi Rich, I think I did not tend to get infections until I got ME. I remember having probably chronic bronchitis around the time I first was ill, but I think that was after (and no more than 2-3 years prior). However my father has chronic infections dating from a very early age, especially respiratory infections; some of his siblings have similar troubles also though none had as much childhood trouble as he had. Asthma runs in the family on his side also. No genetic testing for this has been done.
best,
willowj

 

[Simon]

"Bona fide" syndrome could also mean that ME/CFS is not just a "wastebasket" of people with unexplained fatigue, but a disease with consistent manifestations of immune dysfunction among properly characterized patients.

I'm not sure he would say 'a' single disease, but certainly that as a group something is up biologically. He said on a number of occaisions that CFS is likely to be multiple conditions with mulitple causes, and I think he meant that even using the strictest criteria definitions.