Saturday, 28 February 2015

ME/CFS is real: confirmation if it is needed...

"Scientists discover robust evidence that chronic fatigue syndrome is a biological illness" went the title of the press release for the study by Mady Hornig and colleagues [1] (open-access) detailing an immune 'signature' and also possible staging of the illness.

I couldn't help but wince at some of the media headlines reporting on this study as 'proof' that chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) is a real illness. As I've indicated before on this blog (see here) anyone who has trawled through the collected peer-reviewed research in this area would be hard pressed to arrive at any other conclusion than that CFS/ME is very real and severely impacts on a person's quality of life. I say that accepting that the various definitions and descriptions of the conditions (note the plural) have not always been kind to CFS/ME research and to a large extent, perhaps held back science from making the breakthroughs we've potentially seen with the Hornig results. Hopefully SEID [systemic exertion intolerance disease] might help this process along a little...

Back to the paper:

  • The authorship of the latest research paper includes the great and the good of CFS/ME (and autism) research. Mady Hornig and Ian 'virus hunter' Lipkin have talked quite a bit in recent times about their research commitment to CFS/ME following the whole XMRV de-discovery issue a few years back (see here). José Montoya has similarly impressed with the idea that certain anti-virals *might* be indicated for some cases of CFS/ME (see here).
  • Cytokines - those chemical messengers of the immune system - were the target molecules predominating in the Hornig paper taking into account "diagnosis and other clinical variables". Said immune molecules (over 50 of them) were analysed in nearly 300 participants diagnosed with CFS/ME compared against nearly 350 asymptomatic controls. Authors drew on participants derived from two large US studies of CFS/ME, and those all-important case definitions relied on meeting either or both of the "1994 CDC Fukuda criteria... and the 2003 Canadian consensus criteria for ME/CFS." Participants were also categorised according to how long they had reported experiencing symptoms.
  • Results: "No substantive differences were found between cases and controls when short- and long-duration cases were combined and compared with healthy control subjects." You could see how that sentence could be taken by certain people/groups. But... "Analyses that considered duration of illness revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as a dissociation of characteristic intercytokine regulatory networks." Those describing a shorter duration of illness, as a group, presented with elevated levels of several proinflammatory cytokines than controls or longer illness duration participants. As per the press release: "The association was unusually strong with a cytokine called interferon gamma that has been linked to the fatigue that follows many viral infections, including Epstein-Barr virus (the cause of infectious mononucleosis)." When they say 'unusually strong association', they talk about an odds ratio (OR) of 104.77 (95% CI, 6.975 to 1574.021; P = 0.001) (noting the very wide confidence intervals too).
  • Various other analyses were also applied to the data. "The CART (Classification and Regression Tree) decision tree machine learning method was applied to plasma cytokine and clinical covariate data to find predictors that distinguished ME/CFS cases of short illness duration (≤3 years) from those with a long illness duration (>3 years)." In that respect, the age of participants seemed to play something of a role in the results obtained. But, the authors also acknowledge that this data was "not then validated on an independent test set."
  • Discussions surround the possible reasons for the results obtained, particularly how symptom duration seemed to play an important role in the authors' findings. I do like the idea that "an “exhaustion” of the cytokine-producing cells" might account for why there seems to be a 'burst' of immune system involvement in the early stages of the disease followed by a kind of cytokine burn-out. "The study supports the idea that ME/CFS may reflect an infectious "hit-and-run" event" is one way of looking at it.

What's more to say about this work? Well, we might be seeing 'immune markers' mentioned a little more in CFS/ME research circles in the near future on top of what has been previously reported (see here). Whether specific cytokine profiles might be considered 'diagnostic' for CFS/ME needs quite a bit more replication before anyone gets too ahead of themselves. That being said, as and when such a profile is detected, one might reasonably assume that there could be ways and means to intervene. Another quote: "There are already human monoclonal antibodies on the market that can dampen levels of a cytokine called interleukin-17A that is among those the study shows were elevated in early-stage patients." I say this without making any judgement calls nor providing anything that looks, sounds or smells like clinical/medical advice. I might also advance the idea that other factors might also link into something like IL-17A (see here).

I'm also minded to say that the excitement over immune issues being associated with CFS/ME shouldn't also push other areas back into the shadows as per the very interesting findings being reported on things like mitochondrial function (see here), the gut microbiota (see here) and potential intervention options (see here) to name but a few.

Still, only a few months into 2015 and CFS/ME (or SEID if you wish) is really making some research headlines...

[Update: 2 March 2015: The full IoM report is available here].

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[1] Hornig M. et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Science Advances. 2015; 1: 1: e1400121.

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ResearchBlogging.org Mady Hornig, José G. Montoya, Nancy G. Klimas, Susan Levine, Donna Felsenstein, Lucinda Bateman, Daniel L. Peterson, C. Gunnar Gottschalk, Andrew F. Schultz, Xiaoyu Che, Meredith L. Eddy, Anthony L. Komaroff, & W. Ian Lipkin (2015). Distinct plasma immune signatures in ME/CFS are present early in the course of illness Science Advances, 1 (1) : http://dx.doi.org/10.1126/sciadv.1400121