Abstract
Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts. We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs. Both ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction. Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts. This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.
Highlights
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a highly heterogeneous disease with an unknown aetiopathogenesis
Mitochondrial function is impaired in ME/CFS regardless of disease severity
There were no differences between the moderately and severely affected ME/CFS groups for any of the cellular respiratory parameters (Fig 1). This suggests that mitochondrial function of peripheral blood mononuclear cells (PBMCs) does not correlate with disease severity in ME/CFS and even those moderately affected by the disease have an impairment in bioenergetic function
Summary
Participant informationME/CFS patients were diagnosed by a single physician (JLN) using the Fukuda criteria [3], but all patients adhere to the Canadian Consensus Criteria [15]. Ethical approval for the sample collection from ME/CFS patients was granted from the National Research Ethics Committee North East–Newcastle & North Tyneside 2. The severely affected cohort were either housebound or bedbound by the disease and were unable to attend the clinic even with the use of a wheelchair. This is in line with the recognised classifications of disease severity in ME/CFS as outlined in the NICE guidelines and the International Consensus Criteria (ICC) [16, 17]. Affected patients are mostly housebound by the disease while severely affected patients are mostly bedridden [17]. These seemingly arbitrary categories exist due to the absence of biomarkers in the disease that would be able to distinguish between the disease severity groups and allow more robust definitions to be applied
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