Circulating miRNAs Expression in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Objective
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex
multifactorial disease that causes increasing morbidity worldwide, and many individuals with ME/CFS symptoms remain undiagnosed due to the lack of diagnostic biomarkers. Its aetiology is still unknown, but increasing evidence support a role of Herpesviruses (including Human Herpesvirus 6 species, HHV-6A and HHV-6B) as potential causative agents [1]. Interestingly, the infection by these viruses has been reported to impact the expression of microRNAs (miRNAs) [2, 3], short non-coding RNA sequences, which have been suggested to be epigenetic factors modulating ME/CFS pathogenic mechanisms. Notably, the presence of circulating miRNAs in plasma has raised the possibility to use them as valuable biomarkers for autoimmune diseases [4]. Thus, this study aimed at determining the role of eight miRNAs, which were selected for their previous association with ME/CFS, as potential circulating biomarkers of the disease.
Methods
Forty ME/CFS patients and 20 healthy controls were recruited at the Rīga
Stradiņš University Ambulance outpatient clinic and miRNA presence was quantitatively evaluated in plasma from by specific Taqman assays.
Results and Conclusions
Six out of the eight of the selected miRNAs were differently expressed in
patients compared to controls; more specifically, five miRNAs were significantly
upregulated (miR-127-3p, miR-142-5p, miR-143-3p, miR-150-5p, and miR-448), and one was downmodulated (miR-140-5p). miRNA levels directly correlated with disease severity, whereas no significant correlations were observed with the plasma levels of seven pro-inflammatory cytokines or with the presence/load of HHV-6A/6B genome, as judged by specific PCR amplification. Target genes of altered miRNAs were involved in pathways related to transcriptional control of herpesvirus reactivation, immune response to viral infection, extracellular matrix remodeling, In inflammation, cell viability and immune cell death. The results may open the way for further validation of miRNA as new potential biomarkers in ME/CFS and increase the knowledge of the complex pathways involved in the ME/CFS.