Immune function in Chronic Fatigue Syndrome

Discussions on research pertaining to chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) have appeared now and again on this blog. Whether it be in connection to diagnosis, or prevalence, or the very contentious topic of XMRV, CFS/ME research seems never to be far away from controversy (remembering also the PACE trial and a retort from a colleague of mine, Prof. Malcolm Hooper). While headlines abound about the conditions (notice the use of the plural), one has to remember that accompanying every diagnosis there is a person; and in some cases, the distress and disability that the condition bestows is, quite frankly, life-destroying.

Questions are still being asked about CFS/ME and in particular taken from a recent article - Why can’t medical science figure out chronic fatigue syndrome? I don't profess to have any answers but there are some interesting themes emerging from the peer-reviewed evidence arena.

Two papers recently published offer some interesting areas ideas about the nature of CFS/ME and quite possibly, some core biology related to the conditions. The first paper* by quite a familiar name, Dr Michael Maes (no advert intended) and colleagues suggested that based on several questionnaire and biological criteria, it may be possible to accurately distinguish between CFS, ME and patients with chronic fatigue (CF). The second paper by Brenu and colleagues** (full-text) looked at immune function in patients with CFS/ME over the course of a year and reported on Natural Killer (NK) cell cytotoxic activity and cytokine function over the study period. Dr Maes' research in particular holds some interest for me given his focus on things like gut permeability and use of the amino acid glutamine.

Indeed starting first with the paper by Maes and colleagues*, they looked at whether the reporting of post-exertional malaise (PEM) a key feature of the diagnosis of CFS/ME, could be used to distinguish sub-groups within the diagnoses alongside the measurement of various cytokines as external validating criteria. Their answer: to some degree, ME, CFS and CF are distinct categories; biological markers of IL-1, TNFα, and neopterin also suggested that; and might also be able to distinguish ME/CFS from CF. Interestingly, the authors suggest a potential revision to one of the schedules commonly used - the Fukuda criteria - based on the expression of PEM or not.

The paper by Brenu and colleagues** proceeds down a slightly different path in that they reported significantly reduced NK cell cytotoxic activity consistently across the three testing periods in a small group of patients with CFS/ME compared to non-fatigue controls. They also make mention of that very magical word 'biomarker' given the consistency of their results although I have to question the power of the study.

Aside from the diagnostic delineation of the Maes study, the cumulative results of these two studies stress involvement of the immune system in cases of CFS/ME. I note that the low NK cell activity is something that has cropped up in other conditions, including in autism, as per this paper by Ari Vojdani and colleagues from a few years back. I don't suggest any specific connection on this parameter between the conditions because for example, when it comes to glutathione and CFS/ME, the results don't seem to be comparable to those noted in cases of autism. One has to however be careful at comparing just individual parameters across conditions.

These works add to the considerable body of evidence suggesting that irregularities in immune function seem to coincide with at least some cases of CFS/ME. I know this is probably not new news to those in the know about CFS/ME but for the wider population, where mis-information about the conditions seems still rife, studies like these need to be highlighted if only to move more people into asking the question 'why can't medical science figure out chronic fatigue syndrome?'

* Maes M. et al. Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: Results of supervised learning techniques applied on clinical and inflammatory data. Psychiatry Research. April 2012.

** Brenu EW. et al. Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis. Journal of Translational Medicine. May 2012.
DOI: 10.1186/1479-5876-10-88