Hornig/Lipkin cytokine study out now - press release

[alex3619]

This was a plasma cytokine study. I am guessing at some point they will do a spinal fluid cytokine study. That should address the central/peripheral cytokine issue.

 

[biophile]

This was a plasma cytokine study. I am guessing at some point they will do a spinal fluid cytokine study. That should address the central/peripheral cytokine issue.

Coincidently ...

In fact, the authors tantalizingly noted because ME/CFS appears at least in part to be a central nervous disorder cerebral spinal fluid may very well be a better medium to investigate than peripheral blood. That could suggest we’re due some more important findings in a couple of weeks when the Simmaron Research Foundation/Chronic Fatigue Initiative CSF study is published.

http://www.cortjohnson.org/blog/2015/02/27/clock-ticking-chronic-fatigue-syndrome-hit-run-disorder/

 

[aimossy]

@alex3619 based on the press release on this paper and previous conference info I think this work might be coming in a few weeks.

Edit: I mean the press release said "in the coming weeks"

 

[acer2000]

I would just like to mention that maybe we need a bit of caution in interpreting cytokines as the cause of our symptoms. Firstly from my own experience (and I realise this is N=1), I have had many cytokines tested and many of them have been raised. By treating with a combination of nexavir and abx, I was able to normalise all cytokines for a period of around 6 months - but none of my symptoms improved.

So I take this study, which shows PWC's feel ill no matter whether their cytokines are raised or lowered, as evidence that cytokines are likely not responsible for our symptoms.

I had the same experience. I took antibiotics and it knocked my IL-8 way back down. But my symptoms didn't improve.

 

[Sean]

Interesting times.

 

[oceiv]

I'm not up to reading all 12 pages of this thread right now, so I'm not sure if this question has already been answered.

In the news coverage of this study, I've seen two interpretations of this study. The more prevalent interpretation has been that the study team found biomarkers for only patients who have had ME/CFS for under 3 years, but not for patients who have had the disease for over 3 years. The first interpretation is that this study could lead to a test for patients who have had ME/CFS for under 3 years. The second less common interpretation is that the team found biomarkers for both groups: mostly upregulated immune markers for patients who have had ME/CFS for under 3 years and a burned-out/down-regulated immune system for patients who have had the disease for over 3 years. Which interpretation is correct?

ETA: @Jonathan Edwards @Simon Do you know?

 

[Kati]

CRP and ESR only measure inflammation that includes IL-6 production. That is quite a wide range but by no means all sort. CRP does not go up in lupus a lot of the time.

I don't actually think there is likely to be that much 'inflammation' of a traditional sort in ME but it looks as if there may well be cytokine involving immune reactions. There are lots of immune disease where there is no typical inflammation - immune thrombocytopenia, Grave's disease, anti-phispholipid syndrome etc etc. To understand what is going on here I think we have to move beyond simple terms like inflammation and deal with specific cellular interactions. That requires a considerable knowledge of immunology so it isn't much help in general discussion I am afraid!

@Jonathan Edwards does it mean that rheumatologists would be a good candidate home for medical specialty? Our field so need and deserve a home soemwhere in medicine. See if I mentioned 'cytokines' to my GP, she would roll her eyes and sigh. Not her ballgame.

 

[lansbergen]

I take an immune modulator and an antiviral which have helped me but I'm not convinced this is a primary problem.

The primary problem is the infection.

 

[lansbergen]

Or maybe the pathogens alter gene expression in infected cells?

The one I suspect does for sure.

 

[aimossy]

In case anyone did miss it, the research paper you can read and download PDF here:
http://advances.sciencemag.org/content/1/1/e1400121

 

[adreno]

To my mind this study is quite useful in showing that the immune system is the wrong thing to focus on. We can't make energy normally. There is something wrong with the metabolism.

Well, there certainly seems to be a piece of the puzzle missing. Other diseases involving cytokine abnormalities or microglial activation don't exhibit exertion intolerance/PEM to the degree of ME/SEID.

 

[Marco]

@Simon

Worth noting that half of the sample came from the NIH/'XMRV' cohort where all cases had a viral-like onset. Let's say half of the remaining cohort (CFI one) also had a viral-like onset and three-quarters of cases, but not all, probably have a viral-like illness. Certainly the NIH cohort means this sample is enriched for patients with a viral onset.

I think I'd mentioned before my reservations about the multi-site studies that used cohorts from those specialising in certain patient types and the potential for skewing results.

IFN-gamma drives faster tryptophan degradation, causes cognitive problems?
Which is quite dramatic. I wonder if there is a way of testing this?

Jarred Younger has mentioned the difficulties in getting direct proof of neuroinflammation and I feel that these indirect measures might provide triangulating evidence. From previous reading I'm pretty sure that IDO activity and the metabolites of tryptophan catabolism such and quinolinic and kynurinic acid and neopterin can be measured in CSF and possibly in PBMCs.

There may already be some suggestions in the existing literature :

https://books.google.fr/books?id=s8g3MG9euwQC&pg=PA44&lpg=PA44&dq=quinolinic acid chronic fatigue&source=bl&ots=QSiQ79ppMu&sig=0QTQ-_h_wsh9imaOZQW9c9jY2aM&hl=en&sa=X&ei=w7XyVPzzH4LlaISMgtAD&ved=0CEMQ6AEwAw#v=onepage&q=quinolinic acid chronic fatigue&f=false

Hopefully the Simmaron CSF study is looking at these markers.

 

[Marco]

Yup, one thing I started toying with was that this swathe of cytokine shifts in the early stage might reflect poor HPA control as much as anything. The question then is what is going on later and I cannot work that out.

Re : what is going on later? Possibly not much of anything in respect of peripheral immune dysregulation. If, as mentioned by @Simon the cohort was 'enriched' by those from the XMRV study (selected as having viral onset) it's possible that the post 3 year pattern is actually more representative. As per the Dubbo studies, post viral cases may have an exaggerated and possibly prolonged immune response that does though eventually settle down.

It would be interesting to know how the XMRV cohort breaks down on the pre and post 3 year immune patterns. I'd also be curious to know if they'd received any treatments aimed at the presumed viral infection.

 

[Marco]

Well, there certainly seems to be a piece of the puzzle missing. Other diseases involving cytokine abnormalities or microglial activation don't exhibit exertion intolerance/PEM to the degree of ME/SEID.

I'm not sure that's the case. Fatigue and exercise intolerance are common features of many conditions involving microglial activation and in post-concussion syndrome they talk about exacerbation of symptoms with exertion. Whether it's to the same degree as ME/CFS is debateable but it may also be the case that PEM may be appropriate to describe what is happening in other conditions but hasn't been researched to the same degree as other issues are considered more important?

 

[aimossy]

Anyone looking into cytokine studies in Major Depression? We may be side swiped with this by a certain brigade.

 

[Sidereal]

The primary problem is the infection.

Which infection?

 

[A.B.]

How these cytokine findings differ from the ones seen in major depression is an interesting question. Maybe @Jonathan Edwards can tell us more?

 

[cigana]

Anyone looking into cytokine studies in Major Depression? We may be side swiped with this by a certain brigade.

From what I've read the cytokine issue in major depression is similar to the one in MECFS - there's plenty of evidence things are awry but no clear direction, and results can be inconsistent between labs (as mentioned in this meta analysis).
Interestingly, they also find over-induced and non-induced immune activation when they split into sub groups (melancholic and non-melancholic), see here.
IL-6 tends to stand out quite a bit, but IMO there's not much to take from these studies in terms of identifying an obvious pattern.

 

[MeSci]

Perhaps the results from the gene expression study that Dr Montoya mentioned on the recent conference call might be used to validate, to some extent, the results of the present study (assuming the cohorts are different).

That study looked at the m-RNA from 200 ME/CFS patients and 400 controls. (See this post.)

If the expression of the genes from the Montoya study, corresponding to the cytokines measured in the present study, show the same relative differences between: patients at less than 3 years, more than 3 years, and controls, then the present study might (effectively) be considered at least partially validated in a different set of patients (and likewise Montoya's study similarly cross-validated).

On the other hand, if the gene expression for those same cytokines is different, then that wouldn't necessarily prove things one way or the other, since the levels of the cytokines measured in the present study could be affected after gene expression (i.e., post-transcriptionally).

I've just posted this in the thread you linked to as I got lost and forgot which thread I was in! So it can be answered in either.

Don't worry if you have answered this later in the thread - I hope to finish reading the thread today - but what was the mRNA for? Cytokines? If so, this article I just found may be completely irrelevant but is interesting, as it indicates how dietary components could be used to modulate levels of different cytokines via effects on mRNA.

EDIT - and now I see which message I meant to answer to, I see that it was cytokines that the mRNA was for.

 

[lansbergen]

Which infection?

The zoonose I suspect.