The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease with huge social-economic impact. It has been suggested that immune dysregulation, nitrooxidative stress, and metabolic impairment might contribute to disease pathogenesis. However, the etiology of ME/CFS remains largely unclear, and diagnostic/prognostic disease markers are lacking. Several long noncoding RNAs (lncRNA, > 200 bp) have been reported to play roles in immunological diseases or in stress responses.

Methods: In our study, we examined the expression signature of 10 very long lncRNAs (> 5 kb, CR933609, His-RNA, AK124742, GNAS1-AS, EmX2OS, MIAT, TUG1, NEAT1, MALAT1, NTT) in the peripheral blood mononuclear cells of 44 ME/CFS patients.

Results: LncRNAs NTT, MIAT and EmX2OS levels were found to be significantly elevated in ME/CFS patients as compared with healthy controls. Furthermore, NTT and EmX2OS levels increased with disease severity. Stimulation of human monocytic cell line THP-1 and glioma cell line KALS1 with H2O2 (oxidative stress) and poly (I:C) (double strand RNA, representing viral activation) increased the expression levels of NTT and MIAT.

Conclusions: Our study revealed a ME/CFS-associated very long lncRNA expression signature, which might reflect the regulatory response in ME/CFS patients to oxidative stress, chronic viral infection and hypoxemia. Further investigations need to be done to uncover the functions and potential diagnostic value of these lncRNAs in ME/CFS.

Source: Yang CA, Bauer S, Ho YC, Sotzny F, Chang JG, Scheibenbogen C. The expression signature of very long non-coding RNA in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2018 Aug 17;16(1):231. doi: 10.1186/s12967-018-1600-x. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1600-x (Full article)

Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration

Abstract:

We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify chronic fatigue syndrome (CFS) patients into subgroups. To date, we have shown that stratifying based on the presence or absence of comorbid psychiatric diagnosis leads to a group with evidence of neurological dysfunction across a number of spheres.

We have also found that stratifying based on the presence or absence of comorbid fibromyalgia leads to information that would not have been found on analyzing the entire, unstratified patient group. Objective evidence of orthostatic intolerance (OI) may be another important variable for stratification and may define a group with episodic cerebral hypoxia leading to symptoms.

We hope that this review will encourage other researchers to collect data on discrete phenotypes in CFS to allow this work to continue more broadly. Finding subgroups of CFS suggests different underlying pathophysiological processes responsible for the symptoms seen. Understanding those processes is the first step toward developing discrete treatments for each.

 

Source: Natelson BH. Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration. Front Physiol. 2013 May 20;4:109. doi: 10.3389/fphys.2013.00109. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657628/ (Full article)

 

Chronic tiredness and idiopathic chronic fatigue–a connection?

Abstract:

Evidence is adduced to support the proposal that pathological fatigue is a consequence of impaired capillary blood flow resulting in inadequate oxygen delivery, which is in accordance with physiological concepts of fatigue. Case reports are presented.

Comment in: Chronic fatigue syndrome. [N J Med. 1992]

 

Source: Simpson LO. Chronic tiredness and idiopathic chronic fatigue–a connection? N J Med. 1992 Mar;89(3):211-6. http://www.ncbi.nlm.nih.gov/pubmed/1574202