Chronic fatigue syndrome and circulating cytokines: a systematic review

[JaimeS]

He would seem to be an immunologist.

I wonder if this is because they really thought they needed one, or just to make it sound better...

Agreed and it's a little hypocritical to accuse the review of cherry picking when we're cherry picking what we see as the interesting findings ourselves.

To some degree I agree, @Marco. We also can't ignore legitimately researched studies with which we disagree. However, we are allowed to find certain results more interesting and worthy of discussion than others, without being scientifically unethical.

In my mind, the issue with cherry-picking is when you choose to publish based on certain data while well aware you are ignoring studies that directly relate to your topic of choice. I think there is an inherent understanding that your data would be weakened by what you have chosen not to address.

-J

 

[SOC]

So the question I have is whether it's normal for psychiatrists to do reviews on immunological stuff?

As a former reviewer of scientific papers, I can say this should have raised huge flags. This particular group is NOT knowledgeable in the field they are claiming to provide research in AND they have a massive investment in a null result (not finding physiological differences between PWME and the general population). Before you even read the paper, the background suggests there's something dirty afoot. Why "research" outside your field in an area that could destroy your life's work? To sabotage the evidence base is one likely reason.

Any reviewer worth his/her salt should be asking a lot of questions. Come to think of it.... anyone want to bet whether this was reviewed by immunologists who could actually understand the papers supposedly reviewed in this systematic review, or whether this immunology paper written by psychiatrists was also reviewed by psychiatrists?

 

[Snow Leopard]

Take it or leave it with the review paper in question, but the truth is that the pattern of evidence on cytokines is equivocal regardless...

 

[JaimeS]

Take it or leave it with the review paper in question, but the truth is that the pattern of evidence on cytokines is equivocal regardless...

It certainly isn't well-supported enough to be accepted as factual.

Still, I don't think we're arguing so much that the evidence overwhelmingly supports the point of view that cytokines are dysregulated so much as we are pointing out that the researchers discussed are as deeply emotionally invested in their point of view as we are in ours, and it shows in their supposedly clinical research. We're not publishing studies about our point of view that pretend their studies don't exist!

Well, I should speak for myself: I'm not publishing studies on my point of view that pretend their studies don't exist. Though I'm sure we'd all prefer to pretend that studies this methodologically and ethically unsound did not...

-J

 

[Valentijn]

Take it or leave it with the review paper in question, but the truth is that the pattern of evidence on cytokines is equivocal regardless...

How much have cytokines been tested in ME patients? Very little I bet - it's probably primarily Fukuda studies.

 

[user9876]

Take it or leave it with the review paper in question, but the truth is that the pattern of evidence on cytokines is equivocal regardless...

I've not got access to the paper and so haven't read it but I would have a couple of concerns with such a meta analysis
1) I think there are a number of studies finding differences but in different directions. Looking at just the mean across all the data these differences could cancel out. But really we should be asking a more detailed question of why are the results different - but this is to ask deeper mechanism questions rather than look at statistical aggregation. For example I think there was some discussion on one thread about seasonal changes could that cause differences; or there is Hornig and Lipkin's theory about illness duration. I also wonder if there is just more randomness or perhaps different disease paths that have differing results rather than a simple reproducible change in everyone.
2) I seem to remember some discussion on a thread about the way that cytokines are measured being a little bit unreliable hence you need to measure controls and samples on the same set of runs on the same equipment. If this is the case can you even aggregate statistics.

If anyone has the paper one thing I was wondering is do they aggregate the variance and does that rather than the means indicate differences?

 

[Sidereal]

This is not a meta-analysis, just a systematic review (narrative). No statistical aggregation of results. Meaningless nonsense really.

 

[Gijs]

I don't think that high and consistent raised circulating of TGF is meaningless. This review isn't so bad as some people think.

 

[nandixon]

I would imagine that the P.D. White study, since it is looking at cytokines in their protein form, left out what I think is an important 2011/2012 study by Light, et al., that did show increased IL-10 gene expression (i.e., increased IL-10 mRNA levels) in ME/CFS patients upon exercise:

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome

See this post for more information on that study.

 

[lansbergen]

I would imagine that the P.D. White study, since it is looking at cytokines in their protein form, left out what I think is an important 2011/2012 study by Light, et al., that did show increased IL-10 gene expression (i.e., increased IL-10 mRNA levels) in ME/CFS patients upon exercise:
.

So raised gene expression but no raised protein level.

 

[Valentijn]

Increased expression of a gene is basically a way of saying that more of the protein is being produced.

 

[Snow Leopard]

I didn't think the paper was that bad either, though I admit the paper is neither groundbreaking, nor will have much direct impact on the field. By the way, literally half the discussion is dedicated towards TGF-Beta too.

 

[lansbergen]

Increased expression of a gene is basically a way of saying that more of the protein is being produced.

I disagree. mRNA is the templete for making the protein but that does not mean the protein is made in higher quantity when the messeger is raised.

 

[Valentijn]

I disagree. mRNA is the templete for making the protein but that does not mean the protein is made in higher quantity when the messeger is raised.

It can be. But usually it just means the proteins themselves are produced in higher quantities. If gene expression is having an impact, it isn't due to there being more mRNA without a corresponding change in protein levels.

 

[lansbergen]

It can be. But usually it just means the proteins themselves are produced in higher quantities. If gene expression is having an impact, it isn't due to there being more mRNA without a corresponding change in protein levels.

I want to see mRNA and protein levels in the same paper. measured in the same sample.

 

[Valentijn]

I want to see mRNA and protein levels in the same paper. measured in the same sample.

Yes, that would be ideal. But it seems that measuring proteins is generally easiest, so that is what is usually done. An exception is the Light paper, which appears to have measured mRNA but not proteins.

 

[jimells]

So the question I have is whether it's normal for psychiatrists to do reviews on immunological stuff?

Well their theories are going up in flames while their reputations are in danger of going down the drain. This paper smells of desperation. I almost feel sorry for them. Almost.

 

[jimells]

This particular group is NOT knowledgeable in the field they are claiming to provide research in AND they have a massive investment in a null result (not finding physiological differences between PWME and the general population).

And yet this exactly describes Sir Simon's entry into CFS "research". His website brags about allegedly looking for biochemical mechanisms of the illness. I don't recall that he explains why he thought he was qualified to do that work, but maybe I missed it.

 

[msf]

Haha, nice work A.B.

I also have a question: why should I pay any attention to what four psychiatrists (and one immunologist who hangs around with psychiatrists) think about cytokine production in ME?

 

[msf]

I've just realised that I could have left out 'cytokine production in.'