Welcome to the 70th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.
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Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Sato W, Ono H, Matsutani T, Nakamura M, Shin I, Amano K, Suzuki R, Yamamura T (National Center of Neurology and Psychiatry (NCNP), Japan)
Publication: Brain, Behavior, and Immunity
Link: http://www.sciencedirect.com/science/article/pii/S0889159121001537
Several studies have shown that B cells are abnormal across several measures in ME/CFS. Each B cell expresses a different B cell receptor (BCR) that is specific to a single antigen. BCR repertoire, the diversity of BCR expressed by an individual’s B cells, has been shown to be skewed in immune diseases like systemic lupus erythematosus and multiple sclerosis. This study aimed to determine whether there are similar disease-specific changes in BCR repertoire in ME/CFS.
98 ME/CFS patients (Fukuda, Canadian Consensus, and International Consensus criteria) and 23 healthy volunteers were recruited for this study. Blood samples were collected and peripheral blood mononuclear cells (PBMCs) were isolated. BCR repertoires were analysed using high-throughput genetic sequencing to detect differences in immunoglobulin heavy gene V, D, and J (IGHV, IGHD, and IGHJ, respectively).
The study found that the BCR repertoire of ME/CFS patients was skewed compared to healthy controls, with several IGHV, IGHD, and IGHJ genes upregulated in ME/CFS patients. Further analysis showed an association between patients that indicated that they had an infection-related episode at onset and increased frequency of the IGHV3-30 and IGHV3-30-3 genes.
The authors acknowledged that this study was limited as patients were only recruited from a single-centre and that a larger, multi-centre study would need to be conducted to generalise the findings. They conclude that, with further study, BCR repertoire analysis could be developed as a powerful tool to help diagnose ME/CFS.
Deconditioning does not explain orthostatic intolerance in ME/CFS (myalgic encephalomyelitis /chronic fatigue syndrome)
Authors: van Campen CLMC, Rowe PC, Visser FC (Stichting CardioZorg, Netherlands)
Publication: Journal of Translational Medicine
Link: http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02819-0
Some studies have suggested that OI occurs as a result of deconditioning, however there are conflicting views as to whether it is a cause or consequence of OI. This study aimed to explore the relationship between deconditioning and OI in ME/CFS patients, using retrospective data.
The study included data collected from 199 ME/CFS patients (Fukuda and International Consensus criteria) and 22 healthy controls who had all undergone a cardiopulmonary exercise test (CPET) and head-up tilt test (HUT). Deconditioning was classified according to the peak oxygen consumption (VO2) measured during the CPET, where ≥ 85% = no deconditioning, 65–85% = mild deconditioning, and < 65% = severe deconditioning. OI was confirmed using cerebral blood flow (CBF) measurements taken during the HUT.
Participants with ME/CFS had significantly greater CBF reduction during HUT than healthy controls, but there was no significant difference in CBF reduction between ME/CFS patients who had no, mild or severe deconditioning.
The authors showed using objective measures that there is no correlation between OI and deconditioning in ME/CFS patients, and conclude that their results do not support deconditioning as a cause of OI in ME/CFS.
Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Authors: Wirth KJ, Scheibenbogen C (Charité - Universitätsmedizin Berlin, Germany)
Publication: Journal of Translational Medicine
Link: http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02833-2
These authors have previously hypothesised that ME/CFS is caused by autonomic dysfunction, specifically sympathetic overactivity and β2-adrenergic receptor (β2AdR) dysfunction. β2AdR are important vasodilator receptors in the heart, brain and skeletal muscles, and the authors hypothesised that impaired vasodilation may explain some of the cardiovascular symptoms associated with ME/CFS, such as orthostatic intolerance, hypovolemia and preload failure.
Further, they argued that a bioenergetic disturbance in ME/CFS skeletal muscle sees compensatory vasodilators released in musculoskeletal cells which can explain many other ME/CFS symptoms, such as pain, gastrointestinal disturbance and flu-like symptoms. In this paper, the authors expand their hypothesis to discuss the presumed mechanisms underlying the bioenergetic disturbance in skeletal muscle.
The authors noted that β2AdR stimulate Na+/K- -ATPase in skeletal muscle, and that Na+/K- -ATPase plays a role in muscle fatiguability and recovery. They hypothesise that the observed β2AdR dysfunction also results in insufficient Na+/K- -ATPase stimulation, causing excess sodium in the cells. They claim that this in turn results in calcium overload, affecting the mitochondria and creating a vicious cycle which could explain the exercise intolerance and chronicity seen in ME/CFS. They argue that recovery is rare in ME/CFS because it consists of a series of similarly self-stabilising cycles.
Within the framework of their hypothesis, the authors outline a range of predisposing, precipitating and perpetuating factors for ME/CFS.
Figure: Hypothetical pathomechanisms in skeletal muscle and in cardiovascular system in ME/CFS explaining fatigue and myalgia. Bradykinin (BK), Cardiac output (CO), Orthostatic dysfunction (OD)
Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS
Authors: Jäkel B, Kedor C, Grabowski P, Wittke K, Thiel S, Scherbakov N, … Freitas H (Charité - Universitätsmedizin Berlin)
Publication: Journal of Translational Medicine
Link: http://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02774-w
While cardiopulmonary exercise testing (CPET) is an accepted tool for measuring post-exertional malaise (PEM) in ME/CFS, it is not without risk as it can exacerbate the condition. Hand grip strength (HGS) is a well-established tool used to assess muscle strength and fatigue, and overall physical function. The aim of this study was to investigate repeated HGS measures as a tool for assessing muscle fatigue in ME/CFS, and explore the usefulness of HGS as a potential diagnostic test.
The study included 105 participants with ME/CFS (Canadian Consensus Criteria), 18 participants with cancer-related fatigue (CRF), and 66 age- and sex-matched healthy controls. HGS was measured in two sessions, 60 minutes apart. Participants were required to sit upright during the HGS test, with HGS measured 10 times in each session. Participants completed several questionnaires, including the Bell CFS Disability Scale, SF-36, and Chalder Fatigue Scale. Creatine kinase (CK) and lactate dehydrogenase (LDH) were also measured from a blood sample taken after the second HGS session.
ME/CFS participants had significantly lower maximum and mean HGS compared with healthy controls, and showed greater fatigability and poorer recovery. However, these results were not specific to ME/CFS, as they were also observed in the CRF group.
Lower HGS was correlated with disease severity, PEM and pain in ME/CFS, and was also related to higher CK and LDH in ME/CFS, which the authors suggested reflects the impaired energy production following exertion in ME/CFS.
The authors conclude that HGS could be useful as a diagnostic tool to assess muscle fatigue and fatigability, as well as disease severity in ME/CFS patients.
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