Current Research Provides Insight into the Biological Basis and Diagnostic Potential for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe fatigue illness that occurs most commonly following a viral infection, but other physiological triggers are also implicated. It has a profound long-term impact on the life of the affected person. ME/CFS is diagnosed primarily by the exclusion of other fatigue illnesses, but the availability of multiple case definitions for ME/CFS has complicated diagnosis for clinicians. There has been ongoing controversy over the nature of ME/CFS, but a recent detailed report from the Institute of Medicine (Academy of Sciences, USA) concluded that ME/CFS is a medical, not psychiatric illness. Importantly, aspects of the biological basis of the ongoing disease have been revealed over the last 2–3 years that promise new leads towards an effective clinical diagnostic test that may have a general application. Our detailed molecular studies with a preclinical study of ME/CFS patients, along with the complementary research of others, have reported an elevation of inflammatory and immune processes, ongoing neuro-inflammation, and decreases in general metabolism and mitochondrial function for energy production in ME/CFS, which contribute to the ongoing remitting/relapsing etiology of the illness. These biological changes have generated potential molecular biomarkers for use in diagnostic ME/CFS testing.

Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Researchers and clinicians seem to agree on the urgent need for unbiased, specific diagnostic biomarkers for ME/ CFS to expedite patient diagnosis and treatment, and to abolish disease stigmas for good 45 . There is also a consensus on the advantages that miRNA profiles from different blood fractions, EVs included, exhibit as molecular diagnostic candidates, and yet, a paucity of studies focusing on ME/CFS miRNA profiling is detected 22,[24][25][26][27] .…”

Biomedical Insights That Inform the Diagnosis of ME/CFS

“…The commentary by Sweetman et al [3] nicely follows the general reviews, and squarely addresses the question of whether biomedical science has assisted the clinic, with their views on the biomedical potential of fundamental discoveries augmented by the presentation of data from their own research laboratory. The answer, not surprisingly, is yes and no.…”

A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction

“…Previous studies from our laboratory have used a small cohort of carefully diagnosed ME/CFS patients (the Dunedin cohort) and carried out extensive molecular studies utilizing the principles of precision medicine [33] with strict statistical limits. We have identi ed highly signi cant differences between the patient and control groups [10,26].…”

“…A formal medical diagnosis can only be given after a process of exclusion of other well-established fatigue illnesses, and there is a range of self-reported symptoms that t within one of several available widely de ned sets of clinical criteria for ME/CFS [2,8,9]. There are as yet no agreed diagnostic markers or de nitive clinical tests, the causative agent is not well understood, and the resulting disease pathophysiology is still ill-de ned [10]. Immune dysfunction, chronic viral infection and, recently, metabolic and mitochondrial dysregulation have all been implicated as possible underlying consequences of ME/CFS that sustain the illness.…”

“…SWATH-MS is a recently emerged LC-MS/MSALL strategy that allows systematic, unbiased detection and quantitation of detectable compounds in a sample. Individual proteins, or their patterns of expression or "biosignatures", may yet prove to be valuable biomarkers in a diagnostic assay for ME/CFS and may also prove effective in gauging disease severity, dynamic variations in symptomatology, and longitudinal alterations assessing relapse and recovery phases of the illness, or other important factors like treatments [10,34]. Given that at present, in some countries and among some health practitioners, there is still controversy over whether ME/CFS is a legitimate medical condition, proteome, transcriptome, and metabolome pro les can provide valuable initial objective evidence for the legitimacy of ME/CFS as a distinct disease.…”