Exploring the role of glucocorticoid receptors and co-chaperones in Pemphigus foliaceus stratification.

Glucocorticoids (GC) are the main treatment for pemphigus foliaceus (PF). The effects of GC are mediated through glucocorticoid receptors (GR), with GRα and GRβ being the most significant isoforms. Several molecules are involved in mediating the cellular response to GC and can affect the response to treatment. However, the relationship between sensitivity to GC and the expression of GRα, GRβ, FKBP5, FKBP4, HAT1 and HDAC2 in PF disease has not yet been studied. The purpose of this study was to determine the expression of these molecules in patients with different types of response to treatment. Quantitative real-time PCR was used for gene expression profiling in systemic and cutaneous levels. The protein expression levels of GRα and GRβ and FKBP5 was accomplished through immunohistochemical staining. We studied the association of rs1360780 > FKBP5 SNP with PF disease using TaqMan SNP genotyping. Our findings showed downregulation in the gene expression levels of GRα (p = 0.016), HDAC2 (p = 0.004) and FKBP5 (p = 0.032) genes in PF patients compared to healthy controls in PBMC and an up-regulation in GRα (p = 0.041) and HAT1 (p = 0.008) in remittent patients compared to newly diagnosed patients in skin biopsies. GRα and GRβ proteins were less abundant at the cytoplasmic level in patients (p = 0.048 and 0.005, respectively). The nuclear score of FKBP5 was downregulated in patients (p = 0.028). Moreover, our results revealed that the rs1360780 > T allele is a risk factor to the endemic PF form. This study reported for the first-time the involvement of GRα, GRβ, FKBP5, FKBP4, HAT1 and HDAC2 in PF disease in Tunisian population.