Intraindividual variation of microRNA expression levels in plasma and peripheral blood mononuclear cells and the associations of these levels with the pathogenesis of autoimmune thyroid diseases

Background: microRNAs (miRNAs) circulate in the blood and negatively regulate the expression of mRNAs. Some miRNAs are associated with the development of autoimmune thyroid diseases (AITD); however, there are few reports on the association between miRNA expression and the pathogenesis of AITD or the physiological variations of circulating miRNAs, which are important to examine as biomarkers. Methods: We examined the circadian and day-to-day variations in the expression levels of 5 miRNAs (miR-125a, miR146a, miR-155, let-7e and miR-106a) in plasma and peripheral blood mononuclear cells (PBMC). We also analysed the expression levels of two of these miRNAs (miR-146a and miR-155) in 20 healthy controls, 60 Graves' disease (GD) patients and 50 Hashimoto's disease (HD) patients. Results: For each miRNA, we observed wide intraindividual variation [ coefficient of variation value (CV): 70%100%] compared to measurement error (CV: 20%-40%). In patients with AITD, HD, GD in remission and mild HD, the expression levels of miR-146a in PBMC were increased 296%, 328%, 348% and 464% above the levels in healthy controls, respectively (p = 0.0443 and p = 0.0273, p = 0.0267 and p = 0.0052, respectively). In severe HD, the expression level of miR-155 in plasma was increased to 347% of that in healthy controls (p = 0.0256). Conclusions: The expression levels of miRNAs in plasma and PBMC showed wide intraindividual variation. In addition, miR-146a may be associated with the development of AITD.