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Research Digest 27/7/23

Welcome to the 97th 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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A unique circular RNA expression pattern in the peripheral blood of myalgic encephalomyelitis/chronic fatigue syndrome patients


Authors:
Cheng Y, Xu SM, Takenaka K, Lindner G, Curry-Hyde A, Janitz M (University of New South Wales, Australia)

Publication: Gene

Link: https://www.sciencedirect.com/science/article/abs/pii/S0378111923004092

To date, transcriptomic studies have focused exclusively on linear RNA, not circular RNA (circRNA). CircRNA, which are non-coding RNA, have been implicated in several diseases, including Parkinson’s disease and Alzheimer’s disease. The stability and ubiquitous expression of circRNA make them ideal candidates for diagnostic biomarkers. The aim of this pilot study was to examine the differential expression of circRNA in ME/CFS, both before and after exertion.

This small study consisted of 13 ME/CFS patients (diagnosed according to the Canadian Consensus Criteria) and 11 healthy controls (HC). All participants were female. Participants underwent cardiopulmonary exercise tests (CPETs) on two consecutive days. Blood samples were taken four times over seven days: on days one and two when the CPETs were conducted, and again on days three and seven. CircRNA expression analysis was conducted on the samples.

The number of circRNAs detected in ME/CFS patients was higher than in HC. The number of circRNAs in HC increased after exercise, which was not the case in ME/CFS. The authors also found differential expression of circRNA between the two groups, with 14 circRNAs identified that were highly expressed in ME/CFS, but absent in HC.

The authors acknowledge the very small sample size and single-sex of their sample as key limitations of their study. They conclude that while the field of circRNA research is in its infancy, this area holds potential for diagnostic biomarkers for ME/CFS.

Comparison of serum acylcarnitine levels in patients with myalgic encephalomyelitis/chronic fatigue syndrome and healthy controls: a systematic analysis

 

Authors: Jinushi R, Masuda S, Tanisaka Y, Nishiguchi S, Shionoya K, Sato R, … Ryozawa S (Saitama Medical University International Medical Centre, Japan).

Publication: Journal of Translational Medicine

Link: https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-023-04226-z.pdf

 

ME/CFS remains challenging to diagnose due to the absence of a specific diagnostic test. Prior studies have identified low serum acylcarnitine levels in ME/CFS/SEID patients. This systemic review aimed to investigate differences between ME/CFS patients and healthy controls in relation to serum acylcarnitine, and whether this may act as a surrogate diagnostic test.

Studies were included in the review if samples were taken from ME/CFS patients and healthy controls. After the application of exclusion criteria, seven papers (sampling 403 ME/CFS patients) were included in the final meta-analysis.

From the meta-analysis, the authors found that ME/CFS patients had significantly lower serum acylcarnitine levels when compared to healthy controls. The authors hypothesise that this may be due to impaired mitochondrial fatty acid oxidation cascade, due to a viral infection. Some results indicated that lower acylcarnitine levels may be correlated to fatigue levels however, this was not the primary focus of the analysis being conducted.

The authors propose that the measurement of serum acylcarnitine levels may be useful in assisting with the diagnosis of ME/CFS. They acknowledge several potential limitations to this systematic review, including the lack of standardised diagnostic criteria between the studies included. The authors propose that further investigation of the association between serum acylcarnitine levels in ME/CFS patients and healthy controls may assist in correctly diagnosing more patients with ME/CFS in a timely manner.

Suppressed immune and metabolic responses to intestinal damage-associated microbial translocation in myalgic encephalomyelitis/chronic fatigue syndrome 

 

Authors: Uhde M, Indart AC, Green PHR, Yolken RH, Cook DB, Shukla SK, … Alaedini A  (Columbia University, USA)

Publication: Brain, Behaviour and Immunity – Health

Link: https://doi.org/10.1016/j.bbih.2023.100627

Gut epithelial tissue is in contact with many immunogenic microbial cells and dietary products, which means that compromised intestinal barrier integrity can have wide-ranging immune implications.  These authors investigated (1) whether ME/CFS patients have specific systemic adaptive and innate immune responses, (2) whether they exhibit increased gut epithelial cell damage that may contribute to microbial translocation, (3) whether these immune responses are affected during maximal exercise (which increases intestinal permeability and thus microbial translocation), and (4) whether these patients present metabolic differences when compared to healthy controls.

The authors used two independent cohorts: one at rest (131 ME/CFS patients and 86 healthy controls), and one undergoing an exercise challenge (nine ME/CFS patients and seven healthy controls). All participants with ME/CFS met both the Fukuda and Canadian Consensus Criteria. The humoral immune response was evaluated by measuring plasma levels of IgG, IgA, and IgM antibodies to microbial antigens (lipopolysaccharide (LPS) and flagellin) and dietary antigens (wheat gliadin and milk casein) in the cohort at rest.

When compared to the controls, the ME/CFS group had significantly higher antibody responses to microbial and dietary antigens. They also presented a significantly increased intestinal epithelial cell turnover as shown by plasma concentrations measurements of FABP2 (intestinal fatty acid binding protein). In contrast, plasma levels of LBP (LPS-binding protein) and sCD4 (soluble CD4) showed no significant difference between both groups.

In the cohort undergoing a maximal exercise challenge, the ME/CFS group lacked a significant increase in LBP and sCD14 (soluble CD14) acute-phase responses observed in the control group. ME/CFS patients also presented an increased circulating LPS, providing further evidence for the insufficiency of acute-phase innate immune responses in ME/CFS at neutralising circulating microbial products.  IL-10 levels were significantly increased in ME/CFS during maximal exercise, while no change was observed in the control group. Expected increases in glucose and citrate in response to exercise were lacking in ME/CFS patients.

The authors conclude that this study provides evidence for suppressed immune and metabolic responses to intestinal cell damage in ME/CFS. These dysfunctional responses may be relevant in the context of ME/CFS with regard to susceptibility to infections, flu-like symptoms, gastrointestinal dysfunction, and cognitive deficits. The authors encourage future research into the mechanisms underlying these immune responses. 

 

Empowering change for invisible illnesses 

Authors: Krutsch E

Publication: Pro Bono Australia

Link: https://probonoaustralia.com.au/news/2023/07/empowering-change-for-invisible-illnesses/

Emerge Australia’s CEO, Anne Wilson was recently featured in Pro Bono Australia’s Changemaker profile series. The article provides insight into Anne’s career, from graduating from Stanford University’s Graduate School of Business NFP Leadership program to her 13.5 years as CEO of Kidney Australia. Of her role as CEO of Emerge Australia, Anne said:

“This role is arguably the most important of my career in that Emerge Australia stakeholders (those with ME/CFS and now Long COVID) are among the most neglected, misunderstood and under-diagnosed patient cohort within Australia’s health system. The challenges for patients border on human rights issues. That must change and I am committed to spearheading that change on behalf of our patients.”

“I have never experienced in my professional career a greater number of patients for whom the health system does nothing. The cruelty many people with ME/CFS experience is something I was unaware of. It makes me determined to make a difference for this community.”

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