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.
Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, using the golden standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 
Currently, no biomarkers or established diagnostic tests for ME/CFS exist. In Germany, it is estimated that over 300,000 people are affected by ME/CFS. Research from the United States and the UK shows that patients with ME/CFS are medically underserved, as they face barriers to medical care access and are dissatisfied with medical care.
Multiple studies have shown that peak oxygen consumption is reduced in the majority of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) patients, using the gold standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 
12 out of 382 retrieved references were included. Seven studies were randomized controlled trials (RCTs) with one including three reports (1 RCT, 2 single-arms); others were single-arm trials. Interventions included mindfulness-based stress reduction, mindfulness-based cognitive therapy, relaxation, Qigong, cognitive-behavioral stress management, acceptance and commitment therapy and isometric yoga.
Exact low-resolution electromagnetic tomography (
significant differences occurred immediately post-test, which were most pronounced after 24 hours, particularly in the low alpha (8-10 Hz) and low beta (13-18 Hz) frequency sub-bands. Together, the present findings offer support for EEG source localization techniques to investigate PEM. If confirmed, this study could provide a useful instrument for functional diagnosis and evaluation of treatment outcomes.
Recently launched is the global professional association for medical practitioners, scientists and researchers with myalgic encephalomyelitis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post–coronavirus disease 2019 (COVID-19) syndrome (‘long COVID’) with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
I am the volunteer in charge of the newly created WAMES Instagram account. I joined WAMES as a volunteer because I liked the idea of being able to help others that are in my situation, especially young people like me. Running the Instagram account allows me post about things I wish I would have been able to see when I had ME!
After 2 years of suffering with ME, I made a full recovery and 5 years on from my diagnosis, my life is back to normal (if it was ever normal to begin with!) I am on my way to university to study Biomedical Science and I have started swimming again.
