Unravelling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Gender-specific changes in the microRNA expression profiling in ME/CFS

Amanpreet K Cheema, Leonor Sarria, Mina Bekheit, Fanny Collado, Eloy Almenar-Pérez, Eva Martín-Martínez, Jose Alegre, Jesus Castro-Marrero, Mary A Fletcher, Nancy G Klimas, Elisa Oltra, Lubov Nathanson, Amanpreet K Cheema, Leonor Sarria, Mina Bekheit, Fanny Collado, Eloy Almenar-Pérez, Eva Martín-Martínez, Jose Alegre, Jesus Castro-Marrero, Mary A Fletcher, Nancy G Klimas, Elisa Oltra, Lubov Nathanson

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.

Keywords: exercise; gender; immune function; inflammation; microRNAs; myalgic encephalomyelitis/chronic fatigue syndrome; peripheral blood mononuclear cell.

Conflict of interest statement

The authors confirm that there is no conflict of interest.

© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
miRNA expression profile differences between diagnosed ME/CFS individuals and HCs without stratification by gender or fasting status. Data are shown as normalized counts for ME/CFS (red) and healthy controls (HC; Blue) at T0 for (A) miR‐150‐5p, (B) miR‐4443, (C) miR‐423‐5p, (D) miR‐199‐3p and (E) miR‐130a‐3p, regardless of fasting status. * denotes P < .05 and # denotes FDR < 0.1
FIGURE 2
FIGURE 2
miRNA expression profile differences between diagnosed ME/CFS individuals and HCs at T0. Data are shown as normalized counts for males (♂) and females (♀) ME/CFS (red) and healthy controls (HC; Blue) at T0 for (A) miR‐150‐5p, (B) miR‐4443, (C) miR‐423‐5p, (D) miR‐199‐3p and (E) miR‐130a‐3p, regardless of fasting status. * denotes P < .05 and # denotes FDR < 0.1
FIGURE 3
FIGURE 3
miRNA expression profile differences between diagnosed ME/CFS individuals and HCs in response to exercise challenge. Data are shown as normalized counts for ME/CFS (red) and healthy controls (HC; Blue) at T0, T1 and T2 (non‐fasting) for (A) miR‐150‐5p, (B) miR‐4443, (C) miR‐423‐5p, (D) miR‐199‐3p, (E) miR‐125a‐5p, (F) miR‐223‐3p (G) miR‐130a‐3p, (H) miR‐181a‐5p and (I) miR‐126a‐3p. * denotes P < .05 and # denotes FDR < 0.1
FIGURE 4
FIGURE 4
miRNA expression profile differences between diagnosed ME/CFS females and healthy females in response to exercise challenge Data are shown as normalized counts for ME/CFS (red ♀) and healthy females (HC; Blue ♀) at T0, T1 and T2 (non‐fasting) for (A) miR‐150‐5p, (B) miR‐4443, (C) miR‐423‐5p, (D) miR‐199‐3p, (E) miR‐125a‐5p, (F) miR‐223‐3p, (G) miR‐130a‐3p, (H) miR‐181a‐5p and (I) miR‐126a‐3p. * denotes P < .05 and # denotes FDR < 0.1
FIGURE 5
FIGURE 5
miRNA expression profile differences between diagnosed ME/CFS males and healthy males in response to exercise challenge Data are shown as normalized counts for ME/CFS (red ♂) and healthy males (HC; Blue ♂) at T0, T1 and T2 (non‐fasting) for (A) miR‐150‐5p, (B) miR‐4443, (C) miR‐423‐5p, (D) miR‐199‐3p, (E) miR‐125a‐5p, (F) miR‐223‐3p (G) miR‐130a‐3p, (H) miR‐181a‐5p and (I) miR‐126a‐3p. * denotes P < .05 and # denotes FDR < 0.1

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