The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight studies that have particularly caught our attention.
The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.
Audio Commentary by Dr Katrina Pears
There has been a huge variety in studies this week, with eight new ME/CFS studies and twenty-four new Long Covid studies this week.
We have highlighted one of the ME/CFS studies in more detail below:
Paper four (4) uses in vitro experiments, which is experimental work performed outside of a living organism, such as in a test tube. The study used these laboratory based experiments to look at the role of certain proteins (such as; CD24 and CD38) and energy metabolism in more detail.
This study looked at comparing how people with ME/CFS and healthy controls respond to rapid changes in energy demand, as they have previously found that B cells from ME/CFS patients have an increased expression of CD24. To do this, the study measured the levels of CD24, CD38, CD39, CD73 and mitochondrial mass (MM) following stimulation.
- CD24 (or cluster of differentiation 24) is a protein and a heat stable antigen (HAS), it is a cell adhesion molecule. It is expressed on the surface of most B lymphocytes, neuroblasts and neutrophils. It is an important marker in cancer diagnosis and prognosis as it is expressed by many tumours.
- CD38 is a protein marker of cell activation, it is a molecule that can act as an enzyme with NAD-depleting and intracellular signalling activity, or as a receptor with adhesive functions. It has roles in immunity and inflammation, as well as having a role in inflammatory processes during autoimmunity. Its expression is a prognostic marker for chronic lymphocytic leukaemia.
- CD39 is an enzyme which is responsible, together with CD73, for a cascade converting adenosine triphosphate (ATP, i.e. energy) into adenosine diphosphate (ADP) and cyclic adenosine monophosphate. It regulates immune responses balance by hydrolysing ATP and ADP, it has also been recognized as an “immune checkpoint mediator”. It is a marker of pathogenic CD8+ T cells in cancer and other chronic inflammatory diseases.
- CD73 is also an enzyme (also known as 5’-NT) commonly used to convert AMO to adenosine. In addition to its enzymatic function, CD73 is also a signal and adhesive molecule that can regulate cell interaction with extracellular matrix (ECM) components. It is a novel marker for the diagnosis of benign and malignant salivary gland tumours.
This study confirmed energy metabolism disturbances in B cells in ME/CFS, the study found:
- Proliferating B cells from patients with ME/CFS showed lower mitochondrial mass and a significantly increased usage of essential amino acids compared those from HC.
- There was significant delayed loss of CD24 and increased expression of CD38 following stimulation in ME/CFS compared to controls.
- Immunophenotype results suggested the triggering of a stress response in ME/CFS B cells associated with increased usage of additional substrates to maintain necessary ATP levels.
Unfortunately, only the abstract for this study is available as it undergoes its final formatting (which will hopefully be available soon), therefore, we cannot evaluate the fully strength and findings of this study. We do not know for example; the sample size, collection process of the samples or the diagnostic criteria used. Importantly, we don’t know how these in vitro experiments would correspond to what is happening in the body, where there are many more interactions taking place. Furthermore, it would be interesting to know if this is new experimental work, or further analysis of the work previously conducted by Mensah et al., 2018 which looked at CD24 expression and B cells maturation suggesting variations in energy metabolism.
This work could be an interesting piece of the puzzle in energy metabolism in ME/CFS and provide further channels which warrant investigation.
6. Augmentation of Anaerobic Pentose Phosphate Pathway Dysregulates Tetrahydrobiopterin Metabolism in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) Patients with Orthostatic Intolerance: A Pilot Study
16. Reducing sick leave, improving work ability, and quality of life in patients with mild to moderate Long COVID through psychosocial, physiotherapeutic, and nutritive supportive digital intervention (MiLoCoDaS): study protocol for a randomized controlled trial
20. Effects of cardiorespiratory rehabilitation program on submaximal exercise in patients with long-COVID-19 conditions: a systematic review of randomized controlled trials and recommendations for future studies
Dr Katrina Pears,
The ME Association.