Chronic fatigue syndrome (CFS), also commonly known as Myalgic Encephalomyelitis (ME) and more recently Systemic Exercise Intolerance Disease (SEID), is a debilitating disease of unknown aetiology. The central symptom of CFS is persistent fatigue that lasts a minimum of 6 months and which cannot be alleviated by rest or sleep. Other key symptoms of the disease include, but are not limited to, post-exertional malaise, unrefreshing sleep, memory and concentration problems, lymph node sensitivity, and muscle and joint pain. CFS in its most severe form can leave patients bed-bound for months or even years at a time. Each individual patient experiences the disease differently with differing symptom profiles and variability in the severity of individual symptoms on a day-to-day basis within each patient. Consequences of the disease include significant reductions in quality of life, social isolation, and marked functional disability

Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls. 

This study set out to specifically examine key parameters of mitochondrial function including the two major energy-producing pathways in the cell–glycolysis and oxidative phosphorylation (OXPHOS). Changes in these parameters could indicate a mitochondrial basis for CFS and elucidate pathways in the aetiopathogenesis of the disease and identify potential targets for future study.

The aim of this case-control study was to detect and assess changes in mitochondrial functioning and cellular energy profiles systemically (using peripheral blood mononuclear cells (PBMCs)) from chronic fatigue syndrome patients and healthy controls. PBMCs can be relatively easily accessed via blood collections and were used to assess systemic mitochondrial function in controls and CFS patients due to their systemic exposure.

Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls. Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency. While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003). The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.

The results of this study reflect the results from Hartman et al. in T2DM patients, showing a link between a different disease with fatigue as a core symptom and three OXPHOS parameters; basal respiration and maximal respiration. This indicates that the PBMC bioenergetic abnormalities show a consistent link with fatigue, but whether the abnormalities occur as a result of the fatigue or are the cause of disease remains unknown.

This preliminary research has clearly shown statistically significant differences in the bioenergetic profile of PBMC’s derived from CFS patients when compared to non-diseased control cells. Importantly, these results do not establish whether differences in PBMC energy pathways are a cause or a consequence of CFS, however, this data clearly implies that these cells may play a role in the disease pathway. Further, the use of PBMCs may present a new and valuable model for the subsequent design of novel therapeutic approaches to the treatment of CFS.


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