Persistent fatigue induced by interferon-alpha: A novel, inflammation-based, proxy model of Chronic Fatigue Syndrome, 2018, Pariante et al

fivetowns said:
"Oh crap! This isn't going to go away and looks very bad for us. Oh I know! Let's use our collective resources to plug this paper; it doesn't directly contradict our work on psychological perpetuation but looks at biological triggers for fatigue. We can say: "Yes we supported the PACE trial - but look we also supported this quality piece of biomedical research. See there isn't bias towards psychological CFS research! What are those crazy patients on about?! "
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I wouldn't be surprised if I saw that verbatim as an abstract.
 
strategist said:
Probably the next thing that will happen is that they bring CBT/GET into this, according to the idea that inflammation triggers it but the psyche perpetuates it. That could explain why the SMC is promoting this so heavily, when it normally only promotes CBT/GET junk science. Wessely is the CFS expert at the SMC.
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Maybe they're leaving their "unhelpful illness beliefs" behind and saddle up to "it's biological; AND CBT/GET help". Give them want they want - but don't do it, really. Maybe it's the step into the direction to use CBT/GET as a cure for anything and everything.
 
Inara said:
Maybe they're leaving their "unhelpful illness beliefs" behind and saddle up to "it's biological; AND CBT/GET help". Give them want they want - but don't do it, really. Maybe it's the step into the direction to use CBT/GET as a cure for anything and everything.
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They pretty much already do this. This is basically what anyone who’s actually visited a CBT/GET clinic within the last few years gets told (anyone else on the forum who has?). Your illness is real, it’s not all in the mind, the treatment is GET and CBT.
 
Jonathan Edwards said:
Clearly it is all rather semantic.

However, defining a syndrome like ME or CFS (in the sense of the same as ME) is based on the idea that a specific clinical pattern implies some at least partially unknown causal path. Having a virus at the start is part of the accepted syndrome. Having an injection or two of interferon is not - i.e. the subjects do not have 'wild type ME'. And if one allows interferon induced illness then one probably has to include chemotherapy induced fatigue, cancer in ducked fatigue and all the things that the syndrome of wild type ME is intended to exclude.

What is not clear to me is whether or not the subjects in this study do in fact fit with ME in other respects. Do we know they did not have PEM? The Oxford criteria are over inclusive but it might be that all the subjects would have fitted CCC?
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Hi,

Rather interesting comment left on the ME Association's Facebook page that I certainly hadn't considered before. Someone said they had a M.E. diagnosis, then years later incurred a Hep C infection and were treated with IFN-Alpha, and still have M.E. symptoms and a diagnosis.

The comment appears in the post about the BBC Wales feature on the research and the interview with John Peters and Pariante.

As one of the people who had interferon alpha to get rid of my Hep C 12 years ago, I can confirm I have had ME for 35 years, much longer than I had Hep C. I have several friends who went through the same regime. We all had ME before treatment, and we all still have it.
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Made me wonder some more about the Hep C virus. Presumably, someone could develop ME/CFS symptoms and receive a ME/CFS diagnosis if treatment had failed to induce a recovery.

It was during this interview that John asked Pariante if those with 'persistent fatigue' had PEM of course. The answer was no and neither did the researchers (for some reason that I fail to understand) attempt to apply ME/CFS diagnostic criteria to them.

It might have made things easier - then again it might not if they'd used only Oxford for example - had they taken a little more time to do so and provided some indication of the other symptoms being experienced and the degree of overall disability and how it had affected work/education etc.

This was after all funded by the MRC in their tranche for ME/CFS research. It might have helped make it more relevant.

Russell
 
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Russell Fleming said:
Rather interesting comment left on the ME Association's Facebook page that I certainly hadn't considered before. Someone said they had a M.E. diagnosis, then years later incurred a Hep C infection and were treated with IFN-Alpha, and still have M.E. symptoms and a diagnosis. The comment appears in the post about the BBC Wales feature on the research and the interview with John Peters and Pariante.
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But the point of the IFN-a therapy was to see if they could induce persistent fatigue, not to treat it. I don't think they were ever intending to use IFN-a to treat ME.
 
Lucibee said:
I just want to dissect some of what Carmine Pariante said on the Radio Wales programme yesterday:

And what our research shows is that people who go on to develop chronic fatigue syndrome later on have a hyperactive immune system already even before encountering these immune challenges.

Not sure this is true. It might show that those who mount a strong immune response to their persistent infection without clearing it are more at risk, but did it show "hyperactivity"?
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I think the main point here is that he talked about "people who go on to develop chronic fatigue syndrome later on", but he didn't provide any evidence that any of 18 people with persistent fatigue at 6 months after treatment went on to develop CFS. Now I know it's not always easy to get things exactly right in a live interview context, and Dr. Pariante is not a native speaker of English, but I thought he could have been a bit more careful in his choice of words here.

(Apologies for the home-made blue text formatting, I don't know how to reply and include more than one level of quote.)
 
Lucibee said:
These patients had already had a very strong viral infection (HCV), which is why they were being treated with IFN-alfa at all, so to claim that they were looking at what happens early on in the infection is not true.
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I think the confusion is that a slug of interferon tends to mimic what happens in an acute infection such as flu when the body produces its own slug of interferons. Hep C very often produces silent disease for months or years.

I agree that the idea that subjects with worse fatigue have more active immune responses seems wrong. In flu the immune response is the production of interferon. But in this study the interferon comes from outside. What seems to be different about those with more symptoms is that they are more sensitive to an immune mediator.

As far as I know none of the people involved are actually immunologists and the immunological analysis in general seems pretty simplistic.

What the study might be telling us is that some people's nervous system, or physiology as a whole, is more susceptible to a permanent regulatory resetting by an 'immunological storm'. Immunological storms are known to be capable of producing ill effects. The trial of a T cell stimulant at Northwick Park caused serious harm by releasing cytokines. TNF alpha in too high a dose can worsen mortality from infection. But the susceptibility would lie in receptor-mediated sensitivity rather than 'overactivity' in all these cases.
 
Lucibee said:
Early stage of the illness? The paper doesn't tell us how long these patients had had chronic HCV - just that they were recruited from outpatient clinics across London.
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I think, Pariante refers to chronic fatigue as "the illness", not to the hepatitis.

Eta: here is @Lucibee's transcript (could be worth a separate thread -- I really liked @JohnTheJack's short dialogue with Pariante).
 
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Sasha said:
@EspeMor - this is great news but 'Don’t forget you can use ME Action’s toolkit pinned on top to contact your MP to ask him to attend the debate when it happens'? There are women MPs too! In fact, it's the centenary this year of when the first women got the vote in the UK and the first female MP was elected to parliament. Can we get this language fixed, please?
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Sasha, you're SO right. I have messaged the admin of that page! Cheers!
 
I read the comments on a news article on this research and realized there was something wrong but could not figure out what it was. As usual, Dr. Mark Guthridge, in a mere tweet, explained the problem.

Important thread: This new study below, while important scientifically, doesnt examine #MECFS. Rather it examines a fatiguing condition caused by #cytokine treatment that doesnt involve the hallmark #MECFS symptom: Post Exertional Malaise #PEM
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nah, dont delete. But it does show the big difference between what scientific data might show and media spin! And the work has some positives even if it doesnt specifically examine #MECFS
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dave30th said:
I would say that it might be an intelligent attempt to use interferon induced fatigue to inform general approaches to prolonged fatigue. I don't see why they automatically feel the need or the authority to draw specific comparisons with ME, other than in a highly speculative manner, since we have no idea at all if this "fatigue" resembles what ME patients experience or if any of the other cardinal symptoms are present.
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They know they have screwed up magnificently with PACE and their general denial of ME for last three decades so it is expedient to extrapolate this research on ‘fatigue’ and immune system to ME. It makes them look like they are embracing biomedical model. It would be too much of course to expect them to actually research ME patients using robust criteria, they used Oxford for this, clearly. It really is quite silly in my opinion for this to be seen as any kind of breakthrough. Was brilliant to have @JohnTheJack inject some reality into the proceedings with his composure and intelligence.
 
sTeamTraen said:
I'm feeling slightly guilty about my blog post. On the one hand, evidence of an immune system link would be positive news for patients, but on the other, there really doesn't seem to be anything there.
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Well, there is a "there", it's just old news. So if this is what it takes to make old news seem new, this isn't so bad. But it really needs to be emphasized that this is the case and that the lost decades were someone's fault, someone who needs to be blamed and fired... from a cannon... into the sun... along with a pack of rabid minks.

There has been a suspension of disbelief on this disease. Decades and hundreds of objective clues dismissed as inconsequential. Then the SMC makes some weird push about a study that merely confirms the premise that there definitely are physiological anomalies. I guess that's the "there" happening: suspension of disbelief lifted. Maybe.

It's a bit like a large oil company releasing a study proving they have finally found evidence of climate change and the role of greenhouse gases as if it was new. It's not meant to be news itself, it's just an attempt at saving face. Question is what happens after and does it come with a shift in disease model and research funding.
 
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Lucibee said:
Please no thread splitting! I've already linked to it, and don't want it to disappear into the ether!
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Didn't mean to suggest splitting the thread.

It was just my clumsy manner of saying thank you to @JohnTheJack and also BBC Wales for having him. It would be great to have more dialogues of this kind, I mean well informed people asking excellent questions to not so well informed but highly hyped researchers. (Would be also great if the researchers were well informed, of course).
And thank you, @Lucibee, for doing the transcript.
 
Jonathan Edwards said:
What is not clear to me is whether or not the subjects in this study do in fact fit with ME in other respects. Do we know they did not have PEM? The Oxford criteria are over inclusive but it might be that all the subjects would have fitted CCC?
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I think this is the question. I think all we know is that they have fatigue. So it seems like a nice "proof-of-concept" study--that a prolonged fatigue state can be induced by a short-term stimulus. That applies in broad terms to ME but not in specific ones so the claims being made seem way overblown. And with SMC involved, there would seem to be ulterior motives in this over-hyping or over-comparing to CFS.
 
dave30th said:
That applies in broad terms to ME but not in specific ones so the claims being made seem way overblown. And with SMC involved, there would seem to be ulterior motives in this over-hyping or over-comparing to CFS.
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Yes, the more detail we get on what was said in the Pariente interview the more it seems claims are being made out of context.

As I intimated earlier, I think there is some internal MRC politics involved here. I have to respect confidence with regard to various things I have heard but David Attenborough's 'Dynasty' series comes to mind for some reason.
 
dave30th said:
I think this is the question.
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I don’t know if this is the question.

One of the few useful things we learned from CFS research is that there is a lot of idiopathic chronic fatigue out there and only a very tiny percentage is made up of CFS patients. We also know that a significant proportion of CFS patients do not have ME.

The study tells us that a sample of CFS patients selected by the broad Oxford criteria had more severe fatigue than the patients with persisting fatigue after IFN-alfpha. I also suspect that If the researchers could have diagnosed the patients with persisting fatigue as CFS patients, they would have done so. But they didn’t.

So all in all, I’m pretty confident that these patients with fatigue after IFN-alfpha did not have ME. I see it as an interesting study on persisting fatigue. Learning more about chronic fatigue is relevant because ME/CFS patients have lots of it. But I think we can safely assume that most of the IFN-alpha patients in the study did not have ME.
 
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According to this, https://gtr.ukri.org/projects?ref=MR/J002739/1, which would appear to be the, I'm assuming, funded application for this study and from my skim read it would seem that all the claims made recently are all in line with the original application. So my question is why was a study on chronic fatigue funded with funds meant for CFS? And the obvious answer is that, at the time, and seemingly currently as well, the two things are synonymous to the research team and the funding body.
 
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