A SWATH-MS analysis of ME/CFS peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction, by Eiren Sweetman, Torsten Kleffmann, Christina Edgar, Michel de Lange, Rosamund Vallings & Warren Tate in Journal of Translational Medicine vol 18, no: 365 (2020) [doi.org/10.1186/s12967-020-02533-3]
Research abstract:
Background:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious and complex physical illness that affects all body systems with a multiplicity of symptoms, but key hallmarks of the disease are pervasive fatigue and ‘post-exertional malaise’, exacerbation after physical and/or mental activity of the intrinsic fatigue and other symptoms that can be highly debilitating and last from days to months.
Although the disease can vary widely between individuals, common symptoms also include pain, cognitive deficits, sleep dysfunction, as well as immune, neurological and autonomic symptoms. Typically, it is a very isolating illness socially, carrying a stigma because of the lack of understanding of the cause and pathophysiology.
Methods:
To gain insight into the pathophysiology of ME/CFS, we examined the proteomes of peripheral blood mononuclear cells (PBMCs) by SWATH-MS analysis in a small well-characterised group of patients and matched controls. A principal component analysis (PCA) was used to stratify groups based on protein abundance patterns, which clearly segregated the majority of the ME/CFS patients (9/11) from the controls. This majority subgroup of ME/CFS patients was then further compared to the control group.
Results:
A total of 60 proteins in the ME/CFS patients were differentially expressed (P < 0.01, Log10 (Fold Change) > 0.2 and < −0.2). Comparison of the PCA selected subgroup of ME/CFS patients (9/11) with controls increased the number of proteins differentially expressed to 99. Of particular relevance to the core symptoms of fatigue and post-exertional malaise experienced in ME/CFS, a proportion of the identified proteins in the ME/CFS groups were involved in mitochondrial function, oxidative phosphorylation, electron transport chain complexes, and redox regulation. A significant number were also involved in previously implicated disturbances in ME/CFS, such as the immune inflammatory response, DNA methylation, apoptosis and proteasome activation.
Conclusions:
The results from this study support a model of deficient ATP production in ME/CFS, compensated for by upregulation of immediate pathways upstream of Complex V that would suggest an elevation of oxidative stress. This study and others have found evidence of a distinct pathology in ME/CFS that holds promise for developing diagnostic biomarkers.
In the present study, we identified fifty online forum (Reddit) posts, discussing the personal lived experience of Chronic Fatigue Syndrome during lockdown and the global pandemic. These posts were subject to inductive thematic analysis.
Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME) is a chronic disease with complex pathophysiology and unknown etiology. It occurs both in children and adolescents, as well as in adults, with equal frequency. The clinical course is characterized by progressive fatigue, a significant reduction in the body’s efficiency, lack of relief despite rest, and numerous accompanying symptoms. Pathognomonic symptom for PE is the increase in fatigue after physical or mental exertion and the persistence of these symptoms for several hours or days.
Adolescents with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) appear to be more likely to experience anxiety and/or depression using 
Myalgic encephalomyelitis/chronic fatigue syndrome is characterized by persistent and disabling fatigue, exercise intolerance, cognitive difficulty, and musculoskeletal/joint pain. Post–exertional malaise is a worsening of these symptoms after a physical or mental exertion and is considered a central feature of the illness. Scant observations in the available literature provide qualitative assessments of post–exertional malaise in patients with myalgic encephalomyelitis/ chronic fatigue syndrome. To enhance our understanding, a series of outpatient focus groups were convened.
Two consecutive maximal cardiopulmonary exercise tests (CPETs) performed 24 hr apart 
This article reviews the biological underpinnings of ME/CFS presentations, including the interacting roles of the gut microbiome/permeability, 
Creatine supplementation may recharge creatine stores (at least in the skeletal muscles) but this does not inevitably lead to better clinical features in all PFS (postviral fatigue syndrome) patients. It might help some patients to perform more physical work without negative consequences yet creatine is probably less effective to tackle general fatigue and/or nervous system-specific signs and symptoms of PFS. We are still short of information. Does supplemental creatine even reach the brain in PFS, a major stumbling block for creatine delivery in clinical neurology.
