Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood disease affecting 0.2%–2% of the global population. To gain insight into the pathophysiology of ME/CFS in New Zealand, we examined the transcriptomes of peripheral blood mononuclear cells by RNA-seq analysis in a small well-characterized patient group (10 patients), with age/gender-matched healthy controls (10 control subjects). Twenty-seven gene transcripts were increased 1.5- to sixfold and six decreased three- to sixfold in the patient group (P < 0.01). The top enhanced gene transcripts, IL8, NFΚBIA and TNFAIP3, are functionally related to inflammation, and significant changes were validated for IL8 and NFΚBIA by quantitative polymerase chain reaction (qPCR). Functional network analysis of the altered gene transcripts (P < 0.01) detected interactions between the products related to inflammation, circadian clock function, metabolic dysregulation, cellular stress responses and mitochondrial function. Ingenuity pathway analysis (P < 0.05) provided further insights into the dysfunctional physiology, highlighting stress and inflammation pathways. This analysis provides novel insights into the molecular changes in ME/CFS and contributes to the understanding of the pathophysiological mechanisms of the disease.

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

“…In recent years ME/CFS research has shifted its focus from attempting to identify a universal ‘causative agent’ for the illness, to instead ascertaining the key affected physiology and biological pathways behind the ME/CFS symptom complex. High-throughput molecular analyses including cytokine production [ 12 ], metabolomics [ 13 – 16 ], the microbiome [ 17 – 19 ], epigenetics [ 20 – 23 ], transcriptome [ 24 – 26 ] and proteome investigations [ 27 – 32 ] have provided substantial evidence of immune/inflammation involvement, and, significantly, suggest there are deficits in energy metabolism and mitochondrial function in ME/CFS. While there have been inconsistencies in the evidence for mitochondrial dysfunction, a growing number of research papers are supportive of this hypothesis.…”

Hidden Toxicity of Human Papillomavirus Vaccine Ingredients

“…A recent publication has linked organosiloxane contamination to the ever-expanding reports of metabolic and biochemical disruptions inherent to vague syndromes like CFS/ME [17]. The list of metabolic dysregulations and dysfunctional physiology in CFS/ME has now been expanded to include both transcriptome changes and hypothalamic dysfunction [22,23], abnormalities that can easily be caused by the organosiloxane-induced alterations of epigenetic and microglial functions outlined earlier in this report. Chronicity can easily become the norm for all of the above syndromes and illnesses due to (a) Organosiloxane interference with normal healing processes, and (b) The perpetuation of biochemical and epigenetic disruptions during cell division [17,18].…”

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

“…A transcriptome study of the same ME/CFS and control study group found among genes signi cantly differently expressed in ME/CFS, the three most signi cant and increased were IL8, NFKBIA and TNFAI3P, all functionally related as responders to over-activation of in ammatory NF-KB. STRING (P < 0.01) and ingenuity pathway analysis (P < 0.05) of the biological pathways affected by these changed genes including immune/in ammatory pathways, cellular stress response and oxidative stress, circadian clock function, metabolism and mitochondrial function [26]. The correlating gene transcripts encoding the respiratory complexes, TCA cycle proteins and ATP Synthase subunits were not noted to be signi cantly changed in the ME/CFS transcriptome, so may be regulated by post translational mechanisms to increase their proteins, however similar biological pathways were apparently enriched in both studies.…”

“…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].…”

“…In recent years ME/CFS research has shifted its focus from attempting to identify a universal 'causative agent' for the illness, to instead ascertaining the key affected physiology and biological pathways behind the ME/CFS symptom complex. High-throughput molecular analyses including cytokine production [12], metabolomics [13][14][15][16], the microbiome [17][18][19], epigenetics [20][21][22][23], transcriptome [24][25][26] and proteome investigations [27][28][29][30][31][32] have provided substantial evidence of immune/in ammation involvement, and, signi cantly, suggest there are de cits in energy metabolism and mitochondrial function in ME/CFS. While there have been inconsistencies in the evidence for mitochondrial dysfunction, a growing number of research papers are supportive of this hypothesis.…”