Research Research Digest Research Digest 06/03/20 Welcome to the 42nd 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 at the bottom of this page. 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. Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Authors: Missailidis, D., Sanislav, O., Allan, C.Y., Annesley, S.J., Fisher, P.R. Link: https://www.ncbi.nlm.nih.gov/pubmed/32046336The objective of this current study was to find out if abnormalities found in the cells of ME/CFS patients could be useful blood-based biomarkers of ME/CFS.Blood samples were taken from 48 ME/CFS patients (Canadian Consensus Criteria) and 33 healthy controls. Results from this preliminary investigation suggest that three tests hold potential as diagnostic biomarkers: lymphocyte death rate, mitochondrial respiratory function and signalling activity by the Target Of Rapamycin Complex 1 (TORC1). When the three tests were combined, the authors achieved sensitivity and specificity approaching 100%, and suggest that the combination of tests may be used for an accurate diagnostic test. The authors propose a two-stage diagnostic protocol, due to the time, expertise and expenses associated with lymphoblast isolation and testing. The first stage involves an inexpensive and quick screening test using the frozen lymphocyte death rate. Depending on the results, a patient and clinician can decide whether or not to proceed with the more expensive and time-intensive confirmatory tests (mitochondrial respiratory function and TORC1 signalling activity). The authors report that “our results suggested a test protocol which can discriminate between ME/CFS patients and healthy individuals with near-perfect accuracy.”These research findings show promising potential for finding a clinically-suitable diagnostic biomarker for ME/CFS. However, the results will need to be replicated, and expanded to determine the test’s ability to discriminate ME/CFS from other conditions, before the proposed test protocol’s usefulness can be confirmed. An Isolated Complex V Inefficiency and Dysregulated Mitochondrial Function in Immortalized Lymphocytes from ME/CFS Patients Authors: Missailidis, D., Annesley, S.J., Allan, C.Y., Sanislav, O., Lidbury, B.A., Lewis, D.P., Fisher, P.R.Link: https://www.ncbi.nlm.nih.gov/pubmed/3204117This study investigated differences in mitochondrial function and cellular stress sensing in lymphocytes (a type of white blood cell) of ME/CFS patients versus healthy controls.The researchers immortalised lymphoblasts isolated from 51 ME/CFS patients (Canadian Consensus Criteria) and 22 age-matched controls. Mitochondrial function and energy stress sensing were measured in several ways, including Seahorse extracellular flux analysis, proteomics, and biochemical assays. Results showed that ME/CFS lymphoblasts have a significantly reduced rate of ATP synthesis by Complex V (which is sometimes referred to as ATP synthase) compared to controls. Furthermore, they show that the ME/CFS lymphoblasts compensate for this reduction by upregulating respiratory electron transport, as evidenced by elevations in Complex I oxygen consumption rates (OCR), maximum OCR, spare respiratory capacity, non-mitochondrial OCR and "proton leak" as a proportion of the basal OCR.Overall this study suggests that ME/CFS patients have inefficiencies in mitochondrial function in lymphocytes, and that this may be caused by a dysfunction in Complex V of the electron transport chain. This study also suggests that this dysfunction results in compensatory mechanisms which return ATP synthesis and steady state levels to that of a healthy control in a resting state, but could leave cells unable to respond sufficiently to increased demand for energy. I'm 18 years old and living with three chronic conditions you can't see Link: https://www.sbs.com.au/news/insight/i-m-18-years-old-and-living-with-three-chronic-conditions-you-can-t-see_1 Eighteen year old Chloe describes her journey toward finding her diagnosis and learning to manage ME/CFS, fibromyalgia and endometriosis. “Most fifteen-year olds are carefree, active, and happy teenagers, but I wasn’t. Instead I felt exhausted every day, to the point I was almost bedridden, and battled severe joint and abdominal pain - but no one had any idea why.” Call for papers: "ME/CFS – The Severely and Very Severely Affected" Link: https://www.mdpi.com/journal/healthcare/special_issues/me_cfs_issue There is a call for papers for an upcoming special issue of the journal Healthcare, which will focus on severe ME/CFS. The guest editors for this special issue are well-known ME/CFS researchers and clinicians, Dr Kenneth Friedman, Dr Lucinda Bateman and Dr Kenny De Meirleir. “Our intent is to redefine ME/CFS as the serious disease that it is. Up to this point in time, all literature and case definitions of ME/CFS have excluded severely and very severely affected patients, and diagnosis, patient management, and case definitions have been based on the ambulatory ME/CFS patient. We aim to document, describe, and promulgate what can and should be done for this hidden patient population. By focusing on the severely affected, it is our hope that the pathophysiological nature of the disease will be better accepted and understood, and effective methods of symptom reduction and patient improvement will be placed in the medical literature.“ Deadline for manuscript submissions: 31 December 2020.