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Lipkin and Hornig go hunting for ME/CFS pathogens

by Simon McGrath

red bugFor me, the star attraction of Nancy Klimas’ recent CFS/GWI conference was always going to be Professor Mady Hornig and her talk.

Hornig might not be well known by ME/CFS patients – yet – but her boss is: Ian Lipkin, who so skillfully handled the XMRV ‘dediscovery’ study (which she worked on too). Despite disproving a link with XMRV, Professor Lipkin made clear his belief that ME/CFS was a serious disease that had not received the serious attention it deserved. Even more important – given his stellar record as a scientist – was his commitment to playing a serious role in trying to solve the illness. He’s asked Mady Hornig to lead their hunt for the cause of ME/CFS, so I was hoping for an update on how exactly they were going about the work and when results were likely. 

As well as that, we had a presentation of science that made my eyes pop, as Mady Hornig took us through some of her incredible work in other illnesses where brain and immune system take centre stage too. If she brings these kind of approaches to ME/CFS then I think we will benefit enormously – more on this next week.

First, though, to the world’s largest ever ME/CFS biomedical study: the hunt by Hornig, Lipkin and colleagues for a virus or other pathogen that may cause our illness.

Huge initial studies look for pathogens or tell-tale signs of infection

Work has already started with around 400 patients plus controls, including 200 patients + controls from the CFI pathogen study (Professor Hornig is Principal Investigator for CFI’s Pathogen Discovery and Pathogenesis). If that’s not enough, they are hoping to get funding for up to a further 400 patients and controls. Assuming my maths are right, that makes a mind-boggling maximum of 1,600 subjects: 800 patients and 800 controls. This is a big step up for ME/CFS research.

The major part of the study is looking for pathogens – viruses, bacteria or protozoans both known and unknown. But they are also looking for protein/immune abnormalites in patients, and they even plan to take a look at gene expression too to see if that throws up any clues.

The pathogen hunt has three steps:

  1. Screen for a panel of 18 specific pathogens already implicated in ME/CFS, such as EBV.
  2. If no such pathogens are detected, they move to the heavy-duty phase, basically sequencing all DNA/RNA in the blood, which should identify both known and unknown viruses. This technique has been successfully used by Ian Lipkin in the past to discover new viruses.
  3. To be thorough (and these people are nothing if not thorough) any ‘finds’ from the first two steps will be confirmed by a smaller-scale but more accurate technique.

Final bug hunt

Finally, once they have confirmed candidate pathogens – assuming they find ones that have a statistically significant link with ME/CFS – they will develop new tests specifically for these pathogens.

As a bonus, the heavy-duty sequencing techniques in stage 2 makes it fairly easily to look at gene expression too. Previous attempts to identify unusual patterns of gene expression in ME/CFS patients have found differences, but these have not stood up to the test of replication. Hopefully the much larger cohorts used here will produce more reliable findings, and show which genes go awry with with ME/CFS.

Protein signature for ME/CFS?

The team will also try to define ‘host profiles’, looking for a unique protein signature associated with the illness. If the study does find a robust CFS signature, it could be used for diagnosis – and a validated diagnostic test is almost the Holy Grail of ME/CFS research. The signature could also be used to measure treatment progress.

Yet more high-tech approaches

They are using a fancy technique called ‘multiplexed immunoassay’ to look at over 50 specific proteins that are markers of immune/inflammatory changes, or oxidative stress. Again, the idea is to home in on plausible candidates for disruption in ME/CFS. For a smaller sub-sample, they will look more widely for any abnormality in protein profiles using “Target proteomics Mass Spectroscopy” – Nature’s “2012 Method of the Year”, no less. This approach could throw up proteins no one has yet considered playing a role in ME/CFS, giving new clues to the causes of the illness.

Another good reason to look for protein signatures is to detect general signs of infection. One possible scenario raised by Hornig is that lots of different bugs can trigger ME/CFS, and if that’s the case then each individual pathogen might not show up as statistically significant. (This is to do with statistical power, but you really don’t want to know). Finding the fingerprints of infection or inflammation instead might prove a general link between infection and ME/CFS, even if no individual pathogens can be pinned down for sure.

First results due later this year

The first result for these studies will be submitted to journals in the next few months, with more papers submitted later in the year. By the time the year is out we should have a fairly good idea if there is a strong link between pathogens and ME/CFS.

Professor Hornig concluded by saying that they may not find an infectious agent, it may be an immune change. It could even be something else. But if you look at the scale and cutting-edge nature of their work then, even if it does turn out not to be a pathogen, these are very good people to have on the case.

Aiming to look for genetic factors

heading upstream to the source

Heading upstream to the source

In the Q&A section after her talk, someone asked if Mady Hornig and her team also plan to look for any genes that are associated with ME/CFS. It turns out they don’t have enough samples to look at the whole genome, so instead they would like to use a targeted approach that Hornig calls ‘swimming upstream’.

This involves identifying unusual patterns in proteins and/or gene expression using results from this study, then working backwards to identify which gene could be involved in producing these protein changes. It’s an approach the group has used successfully before, and requires a smaller sample size for robust results.  

A wider look at the whole genome might be also possible at a later date using meta-analysis. This would combine their data with data from other studies – giving sufficient ‘statistical power’ for robust results.

The studies I’ve covered above are hugely impressive, but what grabbed me even more was the rest of Mady Hornig’s presentation, where she discusses some of the extraordinary work she’s done on other hard-to-understand illnesses. She’s very keen on bringing similarly innovative approaches to ME/CFS (assuming the current work doesn’t solve the illness!) – as I describe in my next article, Mady Hornig: How do you solve a problem like CFS?.

 

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{ 65 comments… add one }

  • snowathlete March 1, 2013, 1:47 pm

    Thanks Simon,

    It's great to hear these details! Very well summed up. So pleasing that every time that I hear something more about the pathogens study it is something good. It's really great that they are looking at gene expression too and immune abnormalities too.

    I like everything about this study; its the kind of thing we couldn't have dreamed of a few years ago. Can't wait for it to finish. 2013 really could be our year!

  • jimells March 1, 2013, 2:00 pm

    Thanks for this well-written, informative article. It's refreshing to read about a study that wll actually make a substantial contribution to the knowledge base, instead of the usual junk research whose main endpoint is to avoid the business end of 'publish or perish'.

  • Sasha March 1, 2013, 2:10 pm

    Fantastic, Simon – I've been dying to know what kind of progress they've been making on this! Thanks for such a good summary.

    I'm pleased that they're expecting to start to submit papers in the next few months.

    You're right, we couldn't have expected anything like this a few years ago – XMRV, even though it was a dead end, bought us this opportunity.

  • Simon March 1, 2013, 2:24 pm

    Thanks snowathlete, jimmells and Sasha – glad you liked it!

    The presentation iteself was quite complex but Mady Hornig was enormously helpful answering my many questions so hope it's all correct. And I really hope they can get funding for all the cohorts they would like to study

    snowathlete

    …I like everything about this study; its the kind of thing we couldnt have dreamed off a few years ago. Can't wait for it to finish. 2013 really could be our year!

    jimells

    It's refreshing to read about a study that wll actually make a substantial contribution to the knowledge base, instead of the usual junk research whose main endpoint is to avoid the business end of 'publish or perish'.

    Sasha

    You're right, we couldn't have expected anything like this a few years ago – XMRV, even though it was a dead end, bought us this opportunity.

    I wholeheartedly agree: Mady Hornig and Ian Lipkin are class acts and whatever the findings from the study they will be robust conclusions that others (and hopefully they themselves) can build on.

  • Lotus97 March 1, 2013, 3:12 pm

    I just wanted to say I love that cute pathogen image 😀
    I've recently been having bad reactions to probiotics. I've never had this problem before. I've been wondering if it's related to some pathogen. I stopped probiotics for a month or longer and then once I started is when I started having trouble.

  • LaurieL March 1, 2013, 3:38 pm

    Yeah!!! This is great news!! Thank you for posting this!!

  • Lotus97 March 1, 2013, 5:22 pm

    What's the significance of gene expression and where can I read more about it? I've heard someone mention that methylation affects gene expression which I'm curious about since I'm following a methylation protocol. It's also been referenced in Life Extension magazine in relation to calorie restriction and mimetics. They seem to think it's important, but I don't understand any of it.

  • biophile March 1, 2013, 9:16 pm

    Thanks Simon! Looking forward to the results. I hope the cohort is well-defined too.

    I wish everyone was getting the heavy-duty phase, not just the negatives from the first phase.

    Edit: Simon later clarifies that "20% of those positive in stage 1 get sequenced in stage 2 regardless".

  • Forebearance March 1, 2013, 9:42 pm

    Thank you so much for this article! I've also been dying to know what was going on with this study.

  • Esther12 March 1, 2013, 10:51 pm

    Thanks for that info Simon.

    When reading about this study, I often get a fear that the likely heterogeneous nature of CFS will lead to a misleading negative result. I know that I've seen Lipkin talk about CFS as being likely to have a number of different causes, but when there is reason to think that (for some) abnormal responses to common infections like EBV play some role, then if we do not understand the mechanism by which these responses occur (look at the trouble there's been understanding the role of EBV in MS) a well designed study which fails to find solid relationships could be taken as 'evidence of absence'.

    From what I've read of his work with autism (another difficult area) and his brief work on XMRV, I think Lipkin seems like a great guy to have involved in the science of CFS, and he seems to have a cautious and understanding approach to the politics too… but I've still got a concern about how people at the Science Media Centre could present negative results.

  • Sean March 1, 2013, 11:26 pm

    Are they going to be looking at CNS fluid in the studies? Or just blood?

  • Valentijn March 2, 2013, 1:38 am

    Great article Simon and it's great to have the results of this study to look forward to! Even negative results (which I think are unlikely) are progress, as they narrow down the possibilities. As long as the study is well-run, it'll be useful :)

  • vli March 2, 2013, 2:04 am
    Sean

    Are they going to be looking at CNS fluid in the studies? Or just blood?

    I was just thinking that they must've not considered looking at cerebrospinal fluid or tissue biopsies because it costs lots more $ and is lots more cumbersome.

    A member here brought my attention to the fact that, for instance, hhv6 may not be found in blood but in tissue such as in gut as I myself have shown (i've never shown hhv6 in blood but have super high levels of it in two gut biopsies). So what if this study shows false negatives?

  • Simon March 2, 2013, 4:38 am

    Bit more on cohorts:

    Sean

    Are they going to be looking at CNS fluid in the studies? Or just blood?

    So far, just bloods, but Mady Hornig enthused about Dan Peterson's Cerebro Spinal Fluid samples and hopes to get funding for these too. Peterson has 60 extremely-well defined ME/CFS patients, plus an equal number of healthy controls or 'comparators' i.e. patients with specific illnesses eg MS.

    biophile

    I hope the cohort is well-defined too.

    I think they are. Here's a quote from CFI's Scott Carlson about their cohort in a CFS Central Interview:

    The CFI-sponsored cohort recruitment protocol uses the updated CDC definition and the Canadian Consensus Criteria to identify well-characterized subjects. We also noted the new definition presented at the recent IACFSME conference [International ME Criteria].

    So that's half of the pathogen samples in this study. I'm fairly sure (but not 100%) that most of the remainder are from the NIH XMRV study (that Lipkin & Hornig ran) which used Canadian Consensus Criteria only.

  • maryb March 2, 2013, 4:52 am

    I would have thought Dr Chia's patients would have been of interest – stomach biopsies??

  • Purple March 2, 2013, 5:11 am

    I didn't see in the article who is funding these studies. Is it the CFI? I imagine they would be very expensive!

  • Simon March 2, 2013, 8:34 am
    Esther12

    …I often get a fear that the likely heterogeneous nature of CFS will lead to a misleading negative result.

    I know that I've seen Lipkin talk about CFS as being likely to have a number of different causes, but when tthere is reason to think that (for some) abnormal responses to common infections like EBV play some role, then if we do not understand the mechanism by which these responses occur (look at the trouble there's been understanding the role of EBV in MS) a well designed study which fails to find solid relationships could be taken as 'evidence of absence'.

    From what I've read of his work with autism (another difficult area) and his brief work on XMRV, I think Lipkin seems like a great guy to have involved in the science of CFS, and he seems to have a cautious and understanding approach to the politics too… but I've still got a concern about how people at the Science Media Centre could present negative results.

    Reasonable points, and Mady Hornig and Ian Lipkin have designed the studies to take account of this, at least to some extent.

    First off, they have huge samples (esp if they get funding for 800 patients) which will make it easier to detect a real association, even if there are several sub-groups within CFS (which most people expect there to be). But even more important is their work on protein profiles.

    One possibility Mady Hornig discusses is where many different pathogens cause the illness (eg if it's a much down to the person's genetic make up, and the environment, as it is to any bug). Their specific search for markers of immune response, inflammation and oxidative stress should show if there are general signs of infection in CFS patients vs controls. But also this seach, plus the wider seach of proteins they are doing on a sub-sample, shuold also pick up any general disturbances in the immune system, or other systems in the body.

    So I think it's unlikely that the study would completely find 'evidence of absence' even if no pathogens are definitively found. Mady Hornig's talk was mainly about her work in other hard-to-understand illnesses and the kind of innovative and imaginative work she's done elsewhere strongly suggestss she won't give up even with a negative result – blog coming very soon!

    While there's know controlling how the SMC might spin 'no pathogens linked to CFS' results, dismissing Lipkin's work – let's say they finds no pathogens but do find signs of abmormalities – won't be easy: he's a major-league scientist.

  • Sasha March 2, 2013, 9:25 am

    Did she say anything in her talk about treatments, Simon, if any of this stuff comes up positive?

    I know it's not her area and it would be hard to talk specifically about treatments before the bugs/host end has been done but I wondered if her experience in doing this sort of thing with other diseases had given her any experience about what happens next, once that research is done – does it tend to point to treatments that can be fast-tracked?

  • snowathlete March 2, 2013, 9:54 am
    Simon

    While there's know controlling how the SMC might 'no pathogens linked to CFS' results, dimissing Lipkin's work – let's say they finds no pathogens but do find signs of abmormalities – won't be easy: he's a major-league scientist.

    And Lipkin has experience from XMRV of how ME/CFS stories get negatively spun, so he'll probably be carefull how anything is published, even potential negative aspects.

  • Sasha March 2, 2013, 10:26 am
    snowathlete

    And Lipkin has experience from XMRV of how ME/CFS stories get negatively spun, so he'll probably be carefull how anything is published, even potential negative aspects.

    I just clicked 'like' but that seems hardly adequate for this extremely good point! Just think how Lipkin talked about us at the XMRV press conference. We're in excellent hands.

  • Esther12 March 2, 2013, 11:06 am
    Simon

    Reasonable points, and Mady Hornig and Ian Lipkin have designed the studies to take account of this, at least to some extent.

    Yes – they do seem aware of the potential problems. And they seem good. Hopefully that's enough! CFS just seems like such a difficult diagnosis to do useful research on (to me anyway).

  • Gijs March 2, 2013, 11:44 am

    I do not think they are going to find anything in the blood. The are looking at the wrong place.

  • anniekim March 2, 2013, 1:34 pm

    Hi Simon, thanks for this. I just read cort johnson's piece on Hornig's talk on the simmaron website. He wrote a lot on how Horning suggests an overgrowth of bad gut bacteria could cause immune, stress and Cns problems.

    I couldn't really connect the dots. Was she saying that one possible cause of the immune dysfunction can be traced back to the bad bacteria in the gut? Is the gut just one avenue she is considering? Was there the implication that the bad gut bacteria could be theroot cause or a consequence of immune dysfunction? Many thanks

  • Sasha March 2, 2013, 1:39 pm
    anniekim

    I just read cort johnson's piece on Hornig's talk on the simmaron website.

    Thanks, anniekim – I hadn't seen this. Here's the link:

    http://simmaronresearch.com/2013/03/hornig/

  • anniekim March 2, 2013, 1:42 pm
    Simon

    Bit more on cohorts:

    Sean

    Are they going to be looking at CNS fluid in the studies? Or just blood?

    So far, just bloods, but Mady Hornig enthused about Dan Peterson's Cerebro Spinal Fluid samples and hopes to get funding for these too. Peterson has 60 extremely-well defined ME/CFS patients, plus an equal number of healthy controls or 'comparators' i.e. patients with specific illnesses eg MS.

    biophile

    I hope the cohort is well-defined too.

    I think they are. Here's a quote from CFI's Scott Carlson about their cohort in a CFS Central Interview:

    The CFI-sponsored cohort recruitment protocol uses the updated CDC definition and the Canadian Consensus Criteria to identify well-characterized subjects. We also noted the new definition presented at the recent IACFSME conference [International ME Criteria].

    So that's half of the pathogen samples in this study. I'm fairly sure (but not 100%) that most of the remainder are from the NIH XMRV study (that Lipkin & Hornig ran) which used Canadian Consensus Criteria only.

    Re cohorts, when studies say they use both Canadian and CDC criteria I never understand how this works. Does this mean the patients have to fulfil both case definitions? Doesn't the Canadian supercede the CDC as there are more symptoms in the Canadian criteria over and above the CDC definition? Am I missing something? Thanks

  • Simon March 2, 2013, 1:53 pm
    Lotus97

    What's the significance of gene expression and where can I read more about it? I've heard someone mention that methylation affects gene expression which I'm curious about since I'm following a methylation protocol. It's also been referenced in Life Extension magazine in relation to calorie restriction and mimetics. They seem to think it's important, but I don't understand any of it.

    As I'm sure you know, genes encode proteins – but not all genes are 'turned on', many are dormant, and those that are "on" can lead to production of proteins at different levels from very low levels to very high. Gene expression studie looks at the pattern of protein production in healthy patients and controls to see if there are any differences. Eg are some proteins present in CFS patients but not in controls, or vice versa? Or, more likely, are some genes expressed at very different levels between patients and controls? Any differences can give clues as to what;s going wrong in patients. Bit more from Wikipedia.

    Purple

    I didn't see in the article who is funding these studies. Is it the CFI? I imagine they would be very expensive!

    CFI will be funding the CFI cohort of 200, for both the pathogen study and proteins studies, I think. Someone else will be funding the rest of the patients, and Mady Hornig is trying to get more funding from elsewhere to increase the study size. I think a lot of scientists' time goes into securing funding rather than doing science.

    And yes, I don't think they will be cheap. I remember watching a Lipkin lecture talking about pathogen discovery (not for CFS) where in the Q&A he was asked about applying these techniques to CFS. "I'd love to" he said, "if someone gave me $1million" – though I think the money was for the science not his fees :). Not long after there was talk that a New York philanthropist was in contact with Lipkin, and not that much later the CFI was formed and Lipkin was lined up for the pathogen study. I don't know if that's a conicidence, but I did wonder if the philanthropist was watching that lecture too.

  • Simon March 2, 2013, 2:02 pm

    sorry, struggling a bit to keep up here!

    maryb

    I would have thought Dr Chia's patients would have been of interest – stomach biopsies??

    Interesting point: Mady Hornig did talk about the potential role of the gut. Also, she worked a possible link between the measles virus in the gut and children with autism and gut problems so she's taken that approach before.

    anniekim

    Re cohorts, when studies say they use both Canadian and CDC criteria I never understand how this works. Does this mean the patients have to fulfil both case definitions? Doesn't the Canadian supercede the CDC as there are more symptoms in the Canadian criteria over and above the CDC definition? Am I missing something? Thanks

    The Canadian Criteria are generally narrower than the CDC ones – CFI specificed that patients had to meet both criteria and my guess is they met Canadian they met CDC anyway – but if they only met Canadian they would not have been included.

    anniekim

    Hi Simon, thanks for this. I just read cort johnson's piece on Hornig's talk on the simmaron website. He wrote a lot on how Horning suggests an overgrowth of bad gut bacteria could cause immune, stress and Cns problems.

    I couldn't really connect the dots. Was she saying that one possible cause of the immune dysfunction can be traced back to the bad bacteria in the gut? Is the gut just one avenue she is considering? Was there the implication that the bad gut bacteria could be theroot cause or a consequence of immune dysfunction? Many thanks

    Yes, she was saying that. Cort is ahead of me – I just wrote about her new study, and will write about her other work next week – while Cort got it all into the one article.

  • taniaaust1 March 2, 2013, 5:05 pm

    If Im understanding this study right… those who are easily found to have things like EBV wont then be going throu the High thoughput PCR senquencing? (and also hence the results of their gene expressions wont be included?). :(

    Its the EBV group I'd like to see very rigoreously studied as that is linked to so many ME/CFS cases… maybe those are even more likely to be carrying other things too then the group which wasnt obviously carrying something. Some stand out things may be missed by not looking deeper at this group in the same way as the other group is being looked at.

  • acer2000 March 2, 2013, 10:41 pm
    Sean

    Are they going to be looking at CNS fluid in the studies? Or just blood?

    I participated in this study. The "Columbia" studies are in 3 parts. The first was blood samples for the XMRV study. The second phase was looking for all known and novel pathogens. It was several months ago, but my recollection is that they took blood, tears, rectal swab, and I think one more (either nasal or throat swab – my memory is fuzzy so I don't recall at the moment). The third study was/is supposed to use spinal fluid. At the time I gave my samples for part 2, they were still working out the details for part 3. They may well have sorted it out now.

  • acer2000 March 2, 2013, 10:44 pm
    Esther12

    Thanks for that info Simon.

    When reading about this study, I often get a fear that the likely heterogeneous nature of CFS will lead to a misleading negative result.

    While I have no idea what they will ultimately find, I know that they were very particular about selection for these studies. I have been a patient with my CFS doctor for over 5 years and it wasn't at all guaranteed that I would be selected when I applied. I know they were very specific about controls as well. I was lucky in that they could find someone around my age/sex/location otherwise I wouldn't have been able to participate despite having qualified due to my illness and labs. My impression is that they are very focused on making sure these studies are done correctly.

  • Sean March 2, 2013, 11:01 pm

    Thanks, acer.

    Good to hear.

  • vli March 3, 2013, 1:40 am
    acer2000

    I participated in this study because my doctor is one of the sites. The "Columbia" studies are in 3 parts. The first was blood samples for the XMRV study. The second phase was looking for all known and novel pathogens. It was several months ago, but my recollection is that they took blood, tears, rectal swab, and one more (either nasal or throat swab).

    This is super interesting, I'd never heard of pathogens being looked for in rectal or throat swabs before. Thx acer.

  • acer2000 March 3, 2013, 2:48 am
    vli

    This is super interesting, I'd never heard of pathogens being looked for in rectal or throat swabs before. Thx acer.

    Yeah neither had I, but I am glad that they did multiple samples other than just blood. It increases the chance of finding something. Like others have said, I really hope this thing continues to gain momentum and that someone will do another tissue study like Dr. Chia did. That was smart of him.

  • Valentijn March 3, 2013, 3:41 am
    Gijs

    I do not think they are going to find anything in the blood. The are looking at the wrong place.

    You might be right. But we don't know where something will be found – if we did know, it would be because it had already been found, and no one would need to look! They seem to investigating in a very intelligent and reasonable manner, and I'm glad we've got people with the expertise and funding that are willing to do the research.

  • Simon March 3, 2013, 6:28 am
    taniaaust1

    If Im understanding this study right… those who are easily found to have things like EBV wont then be going throu the High thoughput PCR senquencing? (and also hence the results of their gene expressions wont be included?). :(

    Its the EBV group I'd like to see very rigoreously studied as that is linked to so many ME/CFS cases… maybe those are even more likely to be carrying other things too then the group which wasnt obviously carrying something. Some stand out things may be missed by not looking deeper at this group in the same way as the other group is being looked at.

    Interesting point. I simplified the process slightly and actually 20% of positives from the initial screen will go into high-throughput phase, but most won't. Still, if a lot of people are positive for EBV then they will probably have enough to detect other pathogens, though perhaps not to detect gene expression differences as that tends to need pretty large samples.

    However, these are smart people and if they do find EBV are a substantial group I expect they would want to look at that group in more detail anyway. One of the things that has stood out for me listening to both Lipkin and Hornig is that these are scientists who genuinely want to find out what's going on. They are not looking for ways to show there is no problem. Mady Hornig's work on autism is a good example of this: she looked for and ruled out a link with the measles virus in the gut of children with autism and gut problems – but went on to find a whole load of other abnormalities. More on this in the next blog.

  • Simon March 3, 2013, 6:36 am
    acer2000

    I participated in this study. The "Columbia" studies are in 3 parts. The first was blood samples for the XMRV study. The second phase was looking for all known and novel pathogens. It was several months ago, but my recollection is that they took blood, tears, rectal swab, and I think one more (either nasal or throat swab – my memory is fuzzy so I don't recall at the moment). The third study was/is supposed to use spinal fluid. At the time I gave my samples for part 2, they were still working out the details for part 3. They may well have sorted it out now.

    Thanks so much for this acer, it's great to get first hand accounts from patients. Sounds like you are in the NIH/XMRV cohort rather than the CFI one, since you were sampled for XMRV too. I hadn't realised they had collected more than blood to date. Mady is defintitely trying to get funding for the spinal fluid work, but hasn't secured it yet, as far as I know.

    acer2000

    While I have no idea what they will ultimately find, I know that they were very particular about selection for these studies. I have been a patient with my CFS doctor for over 5 years and it wasn't at all guaranteed that I would be selected when I applied. I know they were very specific about controls as well. I was lucky in that they could find someone around my age/sex/location otherwise I wouldn't have been able to participate despite having qualified due to my illness and labs. My impression is that they are very focused on making sure these studies are done correctly.

    More great info. Having such carefully matched controls will particularly help with the gene expression work as it will reduce the amount of 'noise' since age/sex will be controlled for. Noise is the biggest problem in gene expression, so with matched samples and large cohorts they have a much better chance of finding real differences.

  • anniekim March 3, 2013, 7:15 am
    Simon

    sorry, struggling a bit to keep up here!

    Interesting point: Mady Hornig did talk about the potential role of the gut. Also, she worked a possible link between the measles virus in the gut and children with autism and gut problems so she's taken that approach before.
    The Canadian Criteria are generally narrower than the CDC ones – CFI specificed that patients had to meet both criteria and my guess is they met Canadian they met CDC anyway – but if they only met Canadian they would not have been included.
    Yes, she was saying that. Cort is ahead of me – I just wrote about her new study, and will write about her other work next week – while Cort got it all into the one article.

    Thanks Simon. So have I understood it correctly that Hornig is researching more than one avenue, looking at pathogens in blood such as you have described in this post, but also thinks it may not be viral pathogens involved but gut pathogens so is looking at that too? I look forward to reading your next post on this. Many thanks

  • Sasha March 3, 2013, 7:33 am
    acer2000

    my recollection is that they took blood, tears, rectal swab, and I think one more (either nasal or throat swab – my memory is fuzzy so I don't recall at the moment).

    Tears, wow – I've never heard of tears being collected in any study. What would show up in tears that doesn't show up in other stuff?

    Nasal swab sounds like a good plan – chronic sinusitis is common in PWME and there's interest in general in chronic sinusitis being associated with disruption of the normal microbiome of the stuff in your sinuses.

  • redo March 3, 2013, 9:25 am

    Thanks for the report, Simon!

  • citybug March 3, 2013, 3:40 pm

    Hi, Simon thanks for report. Are the first results going to be published just about general viral testing or have they actually started stage 2? Stage 2 is what I'm waiting for. I hope they keep some of the patients who are positive in stage 1, at least as controls. If we have immune deficiency, and pick up lots of viruses, eliminating the people with other viruses might get rid of your main cohort. I've never had really high titres myself, but I think we need to look at both groups.
    I found Dr. Chia's video very convincing, that we need to look in the tissues. Lerner had also found viruses through biopsies. I think Lipkin said that this throughput method did not work on tissue, too complicated in make up (not if memory got that backward). Someone has been collecting tissues from patients doing standard procedures for years. I think we still have to find some way to get tissues looked at.

  • citybug March 3, 2013, 3:43 pm
    citybug

    Hi, Simon thanks for report. Are the first results going to be published just about general viral testing or have they actually started stage 2? Stage 2 is what I'm waiting for. I hope they keep some of the patients who are positive in stage 1, at least as controls. If we have immune deficiency, and pick up lots of viruses, eliminating the people with other viruses might get rid of your main cohort. I've never had really high titres myself, but I think we need to look at both groups.
    I found Dr. Chia's video very convincing, that we need to look in the tissues. Lerner had also found viruses through biopsies. I think Lipkin said that this throughput method did not work on tissue, too complicated in make up (not if memory got that backward). Someone has been collecting tissues from patients doing standard procedures for years. I think we still have to find some way to get tissues looked at.

    Is there any list of the 18 viruses they looked for?

  • Simon March 3, 2013, 5:13 pm
    citybug

    Are the first results going to be published just about general viral testing or have they actually started stage 2? Stage 2 is what I'm waiting for.

    I hope they keep some of the patients who are positive in stage 1, at least as controls. If we have immune deficiency, and pick up lots of viruses, eliminating the people with other viruses might get rid of your main cohort.

    …I think we still have to find some way to get tissues looked at.

    – Afraid I have no more info on what will be published when.

    – 20% of those positive in stage 1 get sequenced in stage 2 regardless so if they tend to have more viruses, that should show up. If a large group are taken out by the first stage then that would make the group very interesting indeed, and I'm sure there would be further work on it. From a few initial figures Mady showed, only a small proportions were screened out in stage 1, but it looked like early data so final results could be v different.

    – I agree it would be v interesting to look at tissues too, but I suspect this study will be a (pretty-impressive) start, not the final answer.

    citybug

    Is there any list of the 18 viruses they looked for?

    I am sure there is, but I don't know what's on it! Though it probably includes not just viruses but bacteria too such as Borrellia bacteria that trigger lyme disease.

    Not sure I was able to help a huge amount there, sorry!

  • Forebearance March 3, 2013, 6:17 pm
    acer2000

    While I have no idea what they will ultimately find, I know that they were very particular about selection for these studies. I have been a patient with my CFS doctor for over 5 years and it wasn't at all guaranteed that I would be selected when I applied. I know they were very specific about controls as well. I was lucky in that they could find someone around my age/sex/location otherwise I wouldn't have been able to participate despite having qualified due to my illness and labs. My impression is that they are very focused on making sure these studies are done correctly.

    Thank you so much for volunteering for that, Acer.

  • Esther12 March 3, 2013, 6:27 pm
    Forebearance

    Thank you so much for volunteering for that, Acer.

    Yes – thanks to all those patients making the effort to be involved with good quality research.

  • tatt March 4, 2013, 12:17 am

    markers for inflammation and immune dysfunction interest me far more than pathogens. It seems unlikely they'll find a pathogen, although they may find evidence that several pathogens are involved.

    I'm not impressed by Klimas talking about what keeps the illness going as she talks about deconditioning and suggests using a heart monitor in a way that would mean I could hardly go upstairs.

  • Valentijn March 4, 2013, 3:30 am
    tatt

    I'm not impressed by Klimas talking about what keeps the illness going as she talks about deconditioning and suggests using a heart monitor in a way that would mean I could hardly go upstairs.

    Well, I feel a lot better if I don't go up or down a flight of stairs for a week or more. So she really might be onto something in that regard. Those little spurts of over-exertion (or overly-raised heartbeat) might be having a relatively mild effect that is resulting in worse symptoms and reduced ability to do other activities.

    And her talk of deconditioning seems to put it in a rather peripheral status … it's something to avoid if possible, but she also clearly states that PEM is not something to push through if we react badly to a certain level of exertion. And she certainly does not suggest that deconditioning has any central involvement in ME/CFS.

  • Bob March 5, 2013, 11:40 am
  • Esther12 March 5, 2013, 5:04 pm
    Bob

    Simon, congrats, your article has got an endorsement from the CII:
    https://twitter.com/CII722/status/308985339991715841
    https://twitter.com/CII722/status/308985800098447362

    Big up Simon. Nice to see that they're pleased with the articles too.

  • Simon May 31, 2013, 6:38 am

    Breaking news from Invest in ME conference (tweets from Jørgen Jelstad):

    1. They MIGHT have something interesting from the pathogen study, but too early to say:

    Jørgen Jelstad@DeBortgjemte 55m
    #InvestME Progress Hornig-study: much lab work done, but much remaining. Do have candidates -potentially novel- but much too early to say.

    2. Looks like they found a difference between CFS and controls in CSF fluid cytokines
    Pretty sure these are the Peterson/Simmaron samples, 60 patients but controls inc other illness groups too

    #InvestME Hornig: Finds altered patterns of cytokine associative networks in cerebro-spinal fluid in ME/CFS compared to controls..

    Not sure if this is based on CSF still, or on bloods, so sample size uncertain:

    #InvestME Hornig:Show that it is a very different way the immune system as a whole is functioning, or dysfunctioning, in ME comprd to cntrls

  • SOC May 31, 2013, 1:14 pm
    Simon

    Breaking news from Invest in ME conference (tweets from Jørgen Jelstad):

    1. They MIGHT have something interesting from the pathogen study, but too early to say:

    2. Looks like they found a difference between CFS and controls in CSF fluid cytokines
    Pretty sure these are the Peterson/Simmaron samples, 60 patients but controls inc other illness groups too

    Not sure if this is based on CSF still, or on bloods, so sample size uncertain:

    Thanks for the update, Simon! It's all too easy for me to lose track of what's going on in these relatively long-term studies, so it's a huge help to me when someone who's managing to keep up shares their info.:thumbsup: