Overexpression of miR-7977 in CD4+ T cells is associated with multiplex autoimmunity in patients with Addison's disease.

Abstract

Autoimmune Addison's disease (AD) results from a combination of the genetic predisposition, unclear environmental triggers and ensuing immune dysfunction. MicroRNA molecules (miRNAs) are involved in post-transcriptional regulation of numerous target genes, hence may affect the immune function and promote autoimmunity. A deregulated miRNAs profile was reported in several autoimmune conditions. Our study was aimed at a global analysis of miRNA expression in CD4+ T cells from patients with AD. CD4+ T cells were separated from peripheral blood, total RNA enriched in miRNAs extracted, and miRNA expression determined by small RNA sequencing. Global miRNA was investigated in 11 AD subjects and 9 age-matched healthy controls, with subsequent validation of the differentially expressed miRNAs by RT-qPCR in 29 patients and 28 controls. The analysis revealed upregulation of 9 miRNAs and downregulation of miR-509-3p in CD4+ T cells from patients with AD (cut-off fold change (FC) >2, Benjamini-Hochberg P < 0.05). RT-qPCR validation confirmed overexpression of miR-7977 (P < 0.0001, FC = 2.7), miR-374a-5p and miR-1260b (P < 0.05, FC = 1.3 and 1.2, respectively). miR-7977 was upregulated in patients with coexisting autoimmune conditions vs those with isolated AD (P = 0.005, mean FC = 2.2). Moreover, miR-7977 abundance appeared correlated with the number of autoimmune comorbidities (P <0.0001, r = 0.736) and serum autoantibodies against thyroid peroxidase (P < 0.001, r = 0.588). Our study demonstrates upregulated expression of miR-7977 in CD4+ T cells from patients with AD, especially with its polyendocrine form. Further analyses are warranted to replicate our results, establish the marker utility of miR-7977, and elucidate its functional role in autoimmunity.