Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome, by Eiren Sweetman, Margaret Ryan, Christina Edgar, Angus MacKay, Rosamund Vallings, Warren Tate in International Journal of Immunopathology and Pharmacology vol 33 2019 [Published January 11, 2019]
Research 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.
From the conclusion:
Our exploratory approach has enabled us to obtain a rich differentially expressed gene dataset to identify changed biology in ME/CFS. We have identified the circadian rhythm dysregulation pathway as a new possible underlying cause of the unrefreshing sleep, fatigue and metabolic abnormalities seen in ME/CFS. Furthermore, impaired mitochondrial function and resulting oxidative stress, coupled with chronic immune-inflammatory signalling, provides a compelling explanation for the fatigue, cognitive dysfunction and post-exertion malaise experienced in ME/CFS.
Therefore, this study is a further step towards gaining an understanding of the disease process and identifying putative biomarkers to support clinical diagnosis. The biological pathways identified offer a rational explanation of the complex and often multi-systemic nature of ME/CFS.
