859 Molecular characterization of mucosal lichen planus

Abstract

Lichen planus (LP) is an inflammatory mucocutaneous disease. The precise pathogenesis remains elusive. A critical event in the initiation of immune responses in LP lesions is for memory T cells to migrate from the circulation into the skin leading to cytokine/chemokine release (i.e. IFN-γ, IL-1β, IL-6, IL-8, IL-17, JAK3 and TNF-α). We sought to quantitatively examine the differential expression of various molecular mediators in idiopathic mucosal lichen planus and to test if the expression pattern is anatomic site-specific. Using an institutional database, at least 10 LP cases per anatomic site were identified. The histopathological diagnosis was reviewed by the principal investigator (JSV). The tissue was processed for Fluidigm quantitative PCR. Expression patterns of 36 markers based on postulated involvement, including JAK1, JAK2, JAK3, PDE4B, PDE4D, CD271, STAT1, and STAT3, were analyzed for each tissue sample. A pairwise Dunn’s test was used to detect any statistically significant differences in gene expression between anatomic sites. 62/74 (84%) samples (15 lip, 14 gingiva, 13 penis, 5 buccal, 5 anorectal, 4 vulva, 4 tongue) demonstrated quantifiable gene expression. The gene expression of TNNT3 (troponin T type 3; p = 0.003), HSPB6 (heat shock protein, alpha-crystalline-related, B6; p = 0.006), and TNNC2 (troponin C type 2; p = 0.02) was statistically significant between the tongue and gingiva, with the tongue demonstrating higher expression in all three. No other statistically significant anatomic site differences resulted. This is the first study to show differential expression of genetic markers in LP based on anatomic site. Such data may help to further elucidate the pathogenesis of LP and guide future pharmacologic discoveries. Limited literature has suggested PDE4 and JAK inhibition as viable treatments for LP. In our study, the molecular mediators within these pathways demonstrated similar expression among anatomic sites, suggesting treatments may have similar efficacy regardless of disease location.