Reduced glycolytic reserve in isolated natural killer cells from myalgic encephalomyelitis/chronic fatigue syndrome patients: A preliminary investigation

Abstract

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is medically unexplained post-exertional fatigue associated with significant reduction in natural killer cell (NK) cytotoxicity activity. Cytotoxic activity relies on glycolytic flux and mitochondrial respiration to fulfill energetic cellular demands. While mitochondrial dysfunction has been reported in ME/CFS patients, no previous investigation has examined the bioenergetic profile of isolated NK cells from ME/CFS patients. Objective: This study was to determine the metabolic function in resting NK cells from ME/CFS patients. Method: Six ME/CFS patients (aged 50.33 ± 4.95) were age and sex-matched with non-fatigued healthy controls (aged 50.00 ± 5.04). Mitochondrial stress tests measured parameters of mitochondrial function in the NK cells including basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity and bioenergetic health index. Glycolytic stress tests measured parameters of glycolytic function such as glycolytic reserve, glycolysis and glycolytic capacity in isolated NK cells from ME/CFS patients and healthy controls using an extracellular flux analyzer, Seahorse XFp. Result: There was a significant reduction of glycolytic reserve in resting NK cells from ME/CFS patients (0.6 ± 0.07 mpH/ min) compared with healthy control (2.25 ± 1.3 mpH/min). Mitochondrial respiration in resting NK cells did not approach statistical significance between ME/CFS patients and healthy controls. Conclusion: These findings suggest resting NK cells from ME/CFS patients have reduced ability to increase glycolytic flux to respond to high energetic demands for ATP production. Hence, the reduced glycolytic reserves we have identified in isolated resting isolated NK cells should be further investigated to assist in understanding ME/CFS pathogenesis.