547 Reduced regulatory microRNA blood expression profile underlie severe forms of alopecia areata

Background: Alopecia areata (AA) is the most common type of non-scarring inflammatory alopecia. Objectives: To determine which immune and metabolic pathways are disregulated by circulating miRNAs in patients with alopecia areata (AA). Methods: Disease status was classified as mild/moderate (<50% involvement and < 1 yr duration) and severe (=> 1 yr, ≥50% SALT, AT or AU). We interrogated 754 miRNAs on 26 naïve patients and 5 controls using RT-PCR OpenArray technology. Pathway enrichment and drug repurposing analyses were carried out with the GeneCodis and CMaps LINCS, respectively. Results: We identified 19 downregulated miRNAs in patients with severe AA vs mild/moderate and controls, showing an enrichment of pathways related to the immune system (antigen processing and presentation, cytokines, TCR regulation, Th1/Th2, IL-1, IL-4, IL-13), cell cycle, DNA damage repair, cellular response to stress, and post-translational modification of proteins. Some of the specific pathways overrepresented were p53, GFR, NOTCH1, PIP3/AKT, FGFR1, and PDGFR. Finally, 39 drugs potentially capable of reversing this state of dysregulation were predicted, being JAK kinase inhibitors the most important group and, to a lesser extent, antioxidant, antimicrobial and blocker agents of mTOR, FGFR1, VEGF, Raf and endoplasmic reticulum stress response proteins. Conclusions: It would be interesting to carry out prospective studies to determine the value of these circulating miRNA expression profiles in severe forms of AA and their potential value as a prognostic marker in clinical practice.