Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by medically unexplained debilitating fatigue with suggested altered immunological state. Our study aimed to explore peripheral blood mononuclear cells (PBMCs) for microRNAs (miRNAs) expression in ME/CFS subjects under an exercise challenge. The findings highlight the immune response and inflammation links to differential miRNA expression in ME/CFS. The present study is particularly important in being the first to uncover the differences that exist in miRNA expression patterns in males and females with ME/CFS in response to exercise. This provides new evidence for the understanding of differential miRNA expression patterns and post‐exertional malaise in ME/CFS. We also report miRNA expression pattern differences associating with the nutritional status in individuals with ME/CFS, highlighting the effect of subjects' metabolic state on molecular changes to be considered in clinical research within the NINDS/CDC ME/CFS Common Data Elements. The identification of gender‐based miRNAs importantly provides new insights into gender‐specific ME/CFS susceptibility and demands exploration of sex‐suited ME/CFS therapeutics.
Highlights
We found that miRNA expression was different in peripheral blood mononuclear cells (PBMCs) of fasting as compared to non-fasting subjects with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which emphasizes the importance of the National Institute of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS) and Centers for Disease Control and Prevention (CDC)’s newly adopted ME/CFS Common Data Elements (CDE) principles for detailed reporting of subjects’ conditions
Three miRNAs were highlighted here that showed opposite pattern of expression in ME/CFS between fasting and non-fasting: (a) the fasting ME/CFS females and males showed overexpressed miR-223-3p opposite to consistently underexpressed pattern in non-fasting ME/CFS, even in response to exercise, (b) miR-191-5p was overexpressed in both fasting females and males but it was underexpressed in non-fasting ME/CFS males, (c) the consistent higher expression of miR-343-3p in fasting ME/CFS which was not identified in other group and (d) underexpressed miR-548q in both fasting ME/CFS females and males
The results of this study have highlighted: (a) miRNAs that are differentially expressed in ME/CFS, (b) altered miRNAs induced by exercise challenge in ME/CFS, (c) gender influenced miRNAs and their differential expression in response to exercise in disease state and (d) fasting induced miRNA difference, emphasizing the possible role they may play in the ME/CFS-associated disease biology
Summary
The underlying mechanisms associated with the onset and progression of myalgic encephalomyelitis/chronic fatigue syndrome (ME/ CFS), a condition characterized by an abrupt or delayed onset of persistent or relapsing symptomatology, including memory problems, muscle and joint pain, gastrointestinal issues, neurological problems, hormonal imbalance and debilitating fatigue or easy fatigability, remains unclear. Despite of the evidence of gender-related differences in this illness,[21,22] a comprehensive analysis of the effects of an exercise testing on differential miRNA expression between males and females with ME/CFS has not been performed so far. The present study aimed to investigate peripheral blood mononuclear cells (PBMCs) miRNA expression in ME/CFS subjects in comparison with sedentary healthy controls (HCs) under an exercise challenge. We found that miRNA expression was different in PBMCs of fasting as compared to non-fasting subjects with ME/CFS, which emphasizes the importance of the National Institute of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS) and Centers for Disease Control and Prevention (CDC)’s newly adopted ME/CFS Common Data Elements (CDE) principles for detailed reporting of subjects’ conditions
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