Research Digest 18/06/21

Welcome to the 71st 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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Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Authors: Szklarski M, Freitag H, Lorenz S, Becker SC, Sotzny F, Bauer S, …  Scheibenbogen C (Charité – Universitätsmedizin Berlin, Germany)
Publication: Frontiers in Immunology
Soluble cluster of differentiation 26 (sCD26) is a protease expressed on the surface of many cells that serves a wide range of enzymatic and non-enzymatic functions that are known to influence cell activation, vasomotor adaptation and metabolic regulation. sCD26 has been shown to be reduced in multiple autoimmune diseases as well as in a subset of ME/CFS patients. This study aimed to re-evaluate the suitability of sCD26 as a potential diagnostic marker for ME/CFS.
205 ME/CFS patients (Canadian Consensus Criteria) and 98 healthy volunteers donated a blood sample and completed a series of symptom assessment questionnaires. The serum concentrations of sCD26 as well as autoantibodies against several adrenergic, muscarinic, angiotensin and endothelin receptors were measured using ELISA.
The authors found that sCD26 concentrations were significantly lower in females with ME/CFS, but only when compared to both males with ME/CFS and female healthy controls. As a result, the authors could not confirm the diagnostic suitability of sCD26. Correlational analysis of the data did show, however, that in ME/CFS patients who reported an infection-triggered disease onset there was a significant inverse correlation between high levels of alpha 1-adrenergic and M3 muscarinic acetylcholine receptor autoantibodies and low serum sCD26 concentration.
In female ME/CFS patients with an infection-triggered onset, sCD26 concentration was associated with a range of immune markers. Furthermore, in female patients with both infection-triggered and non-infection-triggered ME/CFS, an inverse relationship was found between elevated heart rate during an orthostatic challenge and sCD26 concentrations.
The authors conclude that whilst their findings weren’t able to confirm the diagnostic suitability of sCD26, they do provide some evidence to suggest that sCD26 is linked to immunological and cardiovascular disturbances in ME/CFS.

Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology

Authors: Capdevila L, Castro-Marrero J, Alegre J, Ramos-Castro J, Escorihuela RM (Universitat Autònoma de Barcelona, Spain)
Publication: Sensors
Previous studies have reported an association between ME/CFS symptoms and heart rate variability (HRV) in female ME/CFS patients. This study aimed to determine if the same association is also seen in male ME/CFS patients and to analyse the effect of gender on HRV in ME/CFS.
32 male ME/CFS patients (Fukuda criteria) and 19 healthy male age-matched controls were recruited for this study. Their data was compared with that of 45 female ME/CFS patients (Fukuda criteria) and 25 healthy female age-matched controls from a previous study. Several parameters of HRV were analysed from data collected using a cardiac chest band that was worn continuously and monitored/recorded over three 5-min periods on different days and weeks. Additionally, a variety of self-reported symptom assessment tools were used to evaluate and score all participants for measures of fatigue (FIS-40), sleep quality (PSQI), anxiety and depression (HADS), and neurovegetative symptoms of autonomic dysfunction (NCQ & COMPASS-31).
While male ME/CFS patients consistently showed lower HRV values compared to male controls, unlike female ME/CFS patients, these differences were not significant. Correlational analysis of HRV parameters and self-reported symptoms in males were not as consistent as those in females, with only a few select ME/CFS symptom scores being significantly negatively correlated with any particular HRV parameter. The authors also found that the various HRV parameters correlated differently to the gender and/or health status of participants in the study.
The authors conclude that mobile health technology may be a useful, objective, and non-invasive tool to aid in the diagnosis, monitoring and clinical prediction of fatigue severity, especially in women with ME/CFS. The authors also recommend larger studies to determine if it is possible for the findings in male ME/CFS patients to reach significance.

Post-Exertional Malaise May Be Related to Central Blood Pressure, Sympathetic Activity and Mental Fatigue in Chronic Fatigue Syndrome Patients

Authors: Kujawski S, Słomko J, Hodges L, Pheby DFH, Murovska M, Newton JL, Zalewski P (Nicolaus Copernicus University in Torun, Poland)
Publication:  Journal of Clinical Medicine
Despite post-exertional malaise (PEM) being a key feature of ME/CFS, its underlying mechanism is not yet known. This study aimed to examine differences in aortic stiffness, autonomic nervous system function and severity of fatigue between ME/CFS patients with and without PEM. 
101 ME/CFS patients (Fukuda criteria) were recruited for this study, of which 82 reported experiencing prolonged PEM (PEM), and 19 did not (no-PEM). Participants were excluded if they had an underlying psychiatric illness. Aortic systolic blood pressure was measured by arteriography, and autonomic nervous system functioning was measured at rest in a supine position using a three-channel ECG. Participants also completed questionnaires to measure physical and mental fatigue, depression and anxiety, autonomic symptoms, orthostatic stress, and daytime sleepiness.
The authors found that the PEM group had higher levels of overall fatigue and mental fatigue as well as lower central systolic blood pressure than the no-PEM group. There were no significant differences identified in peripheral blood pressure between the two groups. Higher mental fatigue was related to higher risk of PEM, while higher systolic blood pressure was associated with a lower risk of PEM.
The authors acknowledge that the differences identified between the PEM and no-PEM groups did not remain statistically significant following correction for multiple comparisons. The authors recommend further study be completed to confirm whether higher mental fatigue and sympathetic activity tare related to a higher risk of PEM.

Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Authors: Stanculescu D, Larsson L, Bergquist J (Uppsala University, Sweden)
Publication: Frontiers in Medicine
The authors have previously proposed that a number of endocrine mechanisms that prevent recovery in some intensive care unit (ICU) survivors may contribute to ME/CFS.  This article expands on this by examining treatments for prolonged ICU patients and their potential applicability to ME/CFS. Treatment targets were the suppressed endocrine axes; and the cycle of inflammation, oxidative and nitrosative stress (O&NS) and reduced thyroid function. 
There are two main approaches to the correction of suppressed endocrine axes: treatments using downstream peripheral hormones and those targeting the central axes. Clinical trials have found some evidence of the benefit of peripheral hormones in the treatment of both prolonged ICU and ME/CFS, especially thyroid hormones and hormone combinations, though there is also some concern about the risk of harm from some (such as glucocorticoids) due to their suppression of the endocrine system. While researchers studying both prolonged ICU and ME/CFS have explored reactivating the central endocrine axes, and there have been some clinical trials in both prolonged ICU and fibromyalgia, there have been no clinical trials in ME/CFS.
The second treatment target focussed on breaking the reciprocal relationship cycle of inflammation, O&NS and reduced thyroid hormone function. Again, the provision of thyroid hormones may be promising but requires further research. Trials targeting oxidative stress in critical illness and ME/CFS have focussed on the use of antioxidants and mitochondrial supports but effects have not been large. Studies focussed on the production of pro-inflammatory cytokines and inflammation have yielded mixed results.
The authors noted that considerations must be made for the differences between prolonged critical illness and ME/CFS, particularly the duration and progression of the disease, and potential ME/CFS sub-groups and side-effect susceptibility. Finally, the authors called for collaboration between prolonged critical illness and ME/CFS researchers to allow potential treatments to be identified.
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