349 Hidradenitis Suppurativa Lesions are Characterized by Increased Kinase Signaling Activity

Abstract

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that affects approximately 1 – 4% of the world population and is characterized by recurrent abscesses, nodules, and scars in the apocrine gland-bearing areas. The most frequently affected areas include the armpits, groin, genital area, abdomen, buttocks and under the breasts. Overall, HS is a painful and disfiguring disease and is associated with a significantly impaired quality of life. The underlying mechanisms which drive disease pathogenesis are not completely understood; therefore limited targeted therapies exist for these patients with surgical management being the primary treatment for severe HS. This study was conducted to improve our understanding of the downstream signaling pathways which are differentially expressed in HS patients and may drive disease pathogenesis. RNA was isolated from the skin of 16 healthy subjects and 34 patients with mild to severe HS. The expression of 15 genes was investigated using QuantiGene Plex assay with a focus on signaling molecules. Overall, a majority of the genes tested (12 of 15) showed a significant (p<0.0001) increase in gene expression in the HS patients compared to the healthy subjects. Specifically, HS patients had elevated expression of kinases such as IRAK1 (fold change = 7.3), IRAK2 (fold change = 52.4), SYK (fold change = 4.7) and JAK-STAT signaling molecules JAK1 (fold change = 2.3), JAK3 (fold change = 68.9), TYK2 (fold change = 3.8), STAT1 (fold change = 12.0), STAT2 (fold change = 23.3), STAT3 (fold change = 2.1), STAT5A (fold change = 2.2), STAT5B (fold change = 32.2), and STAT6 (fold change = 8.2), compared to healthy subjects. These data suggest a role for JAK signaling in the pathogenesis of HS and support the rationale for their subsequent antagonism in this population.