Research Research Digest Research Digest 20/05/21 Welcome to the 69th 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. Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome Authors: Metselaar PI, Mendoza-Maldonado L, Yim AYFL, Abarkan I, Henneman P, Velde AAT, … Lopez-Rincon A (Utrecht University, Netherlands) Publication: Scientific ReportsLink: https://pubmed.ncbi.nlm.nih.gov/33633136/ Studies trying to identify biomarkers for ME/CFS through the investigation of mRNA expression have been inconsistent in their findings. These authors suggest that epigenetic factors, such as DNA methylation, may explain some of these inconsistencies. This study aimed to integrate publicly available mRNA expression and DNA methylation data from ME/CFS patients in the hope of finding a novel diagnostic biomarker. The mRNA expression dataset was obtained from the 2006 Critical Assessment of Microarray Data Analysis (CAMDA) conference. This dataset originally measured mRNA expression levels in the PBMC’s of 118 ME/CFS patients (Fukuda criteria). The DNA methylation datasets were obtained from the Gene Expression Omnibus (GEO) - which is an international, publicly available, free database for gene expression and other functional genomics data sets. Four datasets were obtained from the database and includes 99 ME/CFS patients (Fukuda and Canadian Consensus Criteria) and 50 healthy controls. The authors used the recursive ensemble feature selection (REFS) algorithm on the mRNA dataset and identified 23 genes whose changes in expression levels were able to distinguish ME/CFS patients from healthy controls. They were also able to demonstrate that these 23 genes had enhanced DNA methylation compared to controls at 48 sites across the four GEO datasets, and were involved in a range of functions related to intracellular signalling, immune cell receptors, and DNA damage repair. The authors conclude that these 23 genes may serve as good candidates for diagnostic biomarkers, and could be investigated further for potential treatment targets. Cytokine networks analysis uncovers further differences between those who develop myalgic encephalomyelitis/chronic fatigue syndrome following infectious mononucleosis Authors: Jason LA, Cotler J, Islam MF, Furst J, Sorenson M, Katz BZ (Northwestern University, USA)Publication: Fatigue: Biomedicine, Health & BehaviorLink: https://www.tandfonline.com/doi/abs/10.1080/21641846.2021.1915131 Studies have shown that approximately 9-12% of healthy individuals that contract infectious mononucleosis (IM) later go on to develop ME/CFS. This study aimed to identify potential predisposing factors that may lead to the development of ME/CFS following IM infection.4501 college students were enrolled in the study at the start of the school year (timepoint 1; T1, baseline). Students who were later diagnosed with IM were identified (T2) and followed for six months (T3). All participants provided a plasma sample at each timepoint. At T3, students were evaluated to determine if they met one or more of three case definitions of ME/CFS: Fukuda, Canadian Consensus (CCC), and Institute of Medicine (IOM). Students who met more than one set of criteria were categorised as severe ME/CFS (S-ME/CFS) and those who recovered were labelled controls (C). There were 18 participants with S-ME/CFS, 30 with ME/CFS, and 58 Cs.Using the plasma samples collected at baseline, the authors measured and conducted sophisticated network analysis on the cytokines.The authors were able to show distinct differences between the cytokine networks of ME/CFS, S-ME/CFS, and C groups at baseline. In particular, the cytokines networks of those with ME/CFS and S-ME/CFS had more centrality and were more densely interconnected than that of Cs.These findings suggest that there may be biological differences between these three groups and that understanding these differences may help to identify risk factors that predispose individuals to developing ME/CFS following infection. Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome–Results From Open-Label Cyclophosphamide Intervention Study Authors: Sørland K, Sandvik MK, Rekeland IG, Ribu L, Småstuen MC, Mella O, Fluge O (University of Bergen, Norway)Publication: Frontiers in MedicineLink: https://www.frontiersin.org/articles/10.3389/fmed.2021.642710/full The purpose of this study was to examine endothelial function in ME/CFS, using flow-mediated dilation (FMD) and post-occlusive reactive hyperemia (PORH), and to determine if IV cyclophosphamide treatment results in changes to endothelial function in ME/CFS. This study included 40 ME/CFS Norwegian patients (Canadian Consensus Criteria) who were enrolled in this research group’s open label IV cyclophosphamide trial (see Research Digest edition 48). Illness duration was a minimum of 2 years and severity ranged from mild to very severe. Healthy controls were recruited from two other studies conducted by the same authors. There were 66 healthy controls in the FMD cohort and 30 controls in the PORH cohort. FMD and PORH were measured at baseline and again at 12 months following the conclusion of the IV cyclophosphamide trial. At baseline, both FMD and PORH were significantly lower in ME/CFS patients than healthy controls, indicating that the ME/CFS patients had significantly reduced large and small blood vessel endothelial function. While more than half of the ME/CFS patients met the criteria for clinical response to IV cyclophosphamide, there was no relationship between clinical response and changes in endothelial function at the 12 month follow up. The authors acknowledge that a limitation of their study was that they didn’t record the physical activity of healthy individuals, so didn’t control for the effect of inactivity on endothelial function. However, they argue that inactivity alone is not a plausible mechanism for the observed dysfunction, as there was no relationship between endothelial function and disease severity, nor with subjective or objective measures of physical function in ME/CFS patients. Aussie fitness guru opens up about shock diagnosis Publication: A Current AffairLink: https://9now.nine.com.au/a-current-affair/aussie-fitness-queen-tiffiny-hall-debilitating-condition-battle/97565f3e-54d9-45bf-af0b-c2ee15155ee7 Former Biggest Loser coach, Tiffiny Hall, recently appeared on A Current Affair after having revealed that she has been diagnosed with ME/CFS. The 36 year old says she has been dealing with the condition for 18 months and it has taken a toll on her and her family. “It’s been very tough for my whole family. My mum, my dad, my sister, my brother, my husband, they felt helpless, they didn't know how to help. It's not like there's a magic pill or treatment," she said. Emerge Australia’s Dr Heidi Nicholl was also interviewed for the segment and said that recovery to pre-illness level of functioning is uncommon. Segment runs for 5 minutes.