Bioenergetic and proteomic profiling of immune cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: an exploratory study, by Paula Fernandez-Guerra, Ana C Gonzalez-Ebsen, Susanne E Boonen, Julie Courraud, Niels Gregersen, Jesper Mehlsen, Johan Palmfeldt, Rikke K J Olsen, Louise Schouborg Brinth in Biomolecules 2021 Jun 29;11(7):961 [doi: 10.3390/biom11070961]
Research abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction.
Here, we evaluated patients’ symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls.
We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being.
This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency. They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels.
Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.
From study Discussion (4):
…in this study, we aimed to recruit a homogenous group of ME/CFS patients and applied strategies for personalised medicine by performing many tests in a few individuals to shed light on molecular mechanisms of disease in these individuals.
Despite the small sample size, our data indicate a dysregulated mitochondrial metabolism centred on PDH and CoA metabolism, which supports findings from other and larger ME/CFS cohorts [29].
Interestingly, between 35 and 40% of ME/CFS patients experience significant improvement in their health when treated with dichloroacetate, a well-known activator of PDH [74,75]. These open-label studies need further follow-up; however, together with the present study and the previous metabolomics and proteomic studies of independent ME/CFS cohorts, they support dysregulated mitochondrial metabolism as an important feature of ME/CFS pathology.
To some degree, abnormalities in bioenergetics parameters of blood cells have shown to correlate with the severity of ME/CFS symptoms [31,76]. Similarly, coupling efficiency correlated with symptom severity and disease duration in our cohort of ME/CFS patients.
