Frontal fibrosing alopecia (FFA), a clinical variant of follicular lichen planus, is a predominantly postmenopausal, immune-mediated, inflammatory, primary lymphocytic cicatricial alopecia. FFA primarily involves the scalp, facial hair and eyebrows but systematizes to affect widespread body regions. MicroRNAs (miRNAs) have emerged as potential candidates of pathobiologic, diagnostic and therapeutic interest in chronic inflammatory, fibrotic and autoimmune diseases. To explore miRNAs in FFA for their disease relevance we isolated plasma from venous blood from 10 biopsy-proven treatment-naïve FFA cases and 10 matched controls and undertook miRNA expression analysis using the Human Fibrosis miRNA PCR Array (Qiagen). A separate cohort of seven active FFA cases and seven matched healthy controls were ascertained for tissue microRNA analysis and all 14 scalp-biopsy-extracted microRNA samples were subjected to microarray analysis on Affymetrix GeneChip miRNA 4.0 arrays. We generated a list of communities for the two skin tissue networks (cases and controls) and identified cluster centers (exemplars) as representative miRNAs of each community. Twenty exemplars in the control network were significantly enriched in the plasma (control) dataset compared to 27 for FFA. Amongst these, there were 17 miRNAs common in both networks, nine of which were representative in the FFA disease phenotype. Random Forest analysis suggested that four circulating miRNAs (hsa-let-7d-5p, hsa-miR-18a-5p, has-miR-20a-5p and hsa-miR-19a-3p) can discriminate between FFA and controls. Our study of skin and plasma miRNA co-expression highlights circulating miRNAs of potential predictive value as biomarkers that should now be validated in larger cohorts.

Tissue and circulating microRNA co-expression analysis reveals potential involvement of miRNAs in the pathobiology of frontal fibrosing alopecia