Research Research Digest Research Digest 17/09/20 Welcome to the 55th 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. You can also join our community and choose to have the Digest delivered straight to your inbox every fortnight on a Friday afternoon by signing up to our mailing list here. We appreciate the support of everyone who reads the Digest – we encourage regular subscribers to support us with a monthly suggested donation of $2. You can sign up for monthly giving here. Mapping of pathological change in chronic fatigue syndrome using the ratio of T1- and T2-weighted MRI scans Authors: Thapaliya K, Marshall-Gradisnik S, Staines D, Barnden LLink: https://www.sciencedirect.com/science/article/pii/S2213158220302035Studies have shown that the brains of ME/CFS patients exhibit structural and functional differences when examined using different imaging techniques compared to healthy controls. The ratio of T1-weighted to T2-weighted (T1w/T2w) signal intensity in MRI scans has been shown to be a sensitive measure of myelin (white matter) and iron in the brain in recent studies of patients with multiple sclerosis and schizophrenia. The authors of this study aimed to use this T1w/T2w technique to generate whole brain maps of 45 ME/CFS patients (Fukuda criteria) and 27 healthy control participants in order to detect changes in tissue microstructure between the two groups. They studied 46 regions of interest (ROI) across the brain. T1w/T2w values were significantly higher in 20 ROI in ME/CFS patients than in healthy controls, both in white matter and subcortical grey matter structures, indicating higher levels of myelin and/or iron. There were also significant clusters with increased T1w/T2w in ME/CFS, mostly in subcortical grey matter, but also in brainstem and projection white matter tracts. There were no ROI or clusters in which ME/CFS patients had lower T1w/T2w than healthy controls. The authors conclude that the T1w/T2w method is highly sensitive and shows elevated myelin and/or iron in ME/CFS patients relative to healthy controls. Genetic Risk Factors of ME/CFS: A Critical Review Authors: Dibble JJ, McGrath SJ, Ponting CPLink: https://pubmed.ncbi.nlm.nih.gov/32744306/The authors of this paper aimed to critically review the available evidence that genetic factors may increase the risk of developing ME/CFS. Observations that ME/CFS can run in families suggests that genetics may play a role in developing the condition. However, the authors posit that it is unlikely a single genetic variant will cause the condition and that the condition is more likely to be multifactorial, with several genetic variants each slightly increasing the risk of developing ME/CFS. Genome-wide association studies (GWAS) can help identify genetic risk factors for diseases and are especially useful in diseases for which the aetiology is unknown. Because they’re not driven by pre-existing hypotheses or assumptions, they can also uncover unexpected factors contributing to a disease. In order to detect genetic variants with small effects, GWAS need to have large samples, making them expensive to run. While there is evidence that ME/CFS risk is inherited, at least in some people, multiple case-control GWAS of ME/CFS cases have not yet yielded consistently significant associations with any single DNA variants. However, ME/CFS GWAS studies to date have had significant flaws, such ME/CFS cases identified by self-report only (with no use of diagnostic criteria to ensure a homogenous sample), small sample sizes, permissive thresholds for determining significance or confounding factors which had not been accounted for.The authors, therefore, propose that large GWAS focused on discovering the biomolecular mechanisms of ME/CFS are overdue. They suggest that results from these studies, once replicated, would: Increase insight into genes, cellular processes and tissues or cell types that causally change risk for ME/CFS Detect genetic signals that ME/CFS shares with other diseases Help stratification of ME/CFS subtypes Improve how health professionals and the general public perceive ME/CFS by adding further evidence that ME/CFS is a biomedical disorder One of the authors of this paper is also lead investigator of the DecodeME project, a UK ME/CFS GWAS which recently received £3.2m funding from the UK‘s Medical Research Council (MRC) and National Institute for Health Research (NIHR). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption Author: Tölle M, Freitag H, Antelmann M, Hartwig J, Schuchardt J, van der Giet M, Eckardt K, Grabowski P, Scheibenbogen CLink: https://www.mdpi.com/2077-0383/9/8/2443/htmThere is some evidence to suggest that ME/CFS with an infection-triggered onset may involve a dysfunction of ß2-adrenoreceptor antibodies (ß2AR-AB). Immunoadsorption (IA) is a blood purification process which uses specific adsorbers to selectively remove immunoglobulins (antibodies) from the blood, and can be an effective treatment for autoimmune conditions. In a small 2018 study, these authors found that IA reduced immunoglobulin G (IgG) and ß2AR-AB levels in ME/CFS patients, leading to clinical improvement. In this follow-up study, the researchers selected five participants from their previous study to attempt to replicate the efficacy of using IA to reduce ß2AR-AB and treat ME/CFS. The five participants met the Canadian Consensus Criteria (CCC), had an infectious onset and experienced improvement following the original IA treatment. The researchers noted in their previous study that IA increased fatigue in some ME/CFS patients, so this study used a modified protocol in which the treatment was spread out to improve tolerability. The altered IA treatment protocol was well tolerated. There was a 80-90% reduction in total IgG and ß2AR-AB, and four out of the five patients reported improvement in several clinical symptoms lasting for six to twelve months.This small trial provides further evidence of the efficacy of IA as a possible treatment for ME/CFS, as it has been for other conditions in which auto-antibodies play a role. The authors acknowledge that the small sample and lack of placebo control are limitations of this study, and that a randomised controlled trial is needed to study this treatment approach. OPINION: Long-term effects of virus shine a light on chronic fatigue sufferers Author: Green SLink: https://www.theage.com.au/lifestyle/health-and-wellness/long-term-effects-of-virus-shine-a-light-on-chronic-fatigue-sufferers-20200907-p55t9q.html?fbclid=IwAR3yB-hB53EIa--BJPwBGG7VPwWQ0KMoBxF_1ZD7kiSAKa7ZGX20E2pPWYoIn a powerful opinion piece published in The Age newspaper on September 7 2020, journalist and long-time ME/CFS patient Sue Green highlights the symptomatic parallels experienced by people living with ME/CFS and those who contract COVID-19 and never recover to full health, and the fact that only now are experts calling for more research to better understand ME/CFS.