227 Primary Changes in the Development of Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease of the apocrine gland-rich (AGR) skin region. Although the immune alteration in lesional HS skin is well-characterized the initial steps of the disease are not fully understood. We aimed to investigate the immune characteristics of non-lesional HS skin, representing the first stage of HS development, and to compare that with lesional HS skin as well as healthy AGR region. Our main focus was to study the immune components showing significantly different levels between AGR and lesional HS skin samples in our previously published report. Immune cell counts (T cells, dendritic cells, macrophages), T helper (Th)1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL-10, IL-23A, TGFB1, RORC, CCL20), keratinocyte (KC)-related sensors, mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP), proinflammatory molecules (TLR2, TLR4, IL-1B, IL6, TNFA, IL-23A) and chemokines (CCL2) were investigated in the three sample groups by multiple mRNA (RNAseq and RT-qPCR) and protein-based (IHC and IF) methods. According to our findings, when comparing non-lesional HS and AGR skin, KC-derived antimicrobial peptides were highly upregulated in the non-lesional HS skin. The epidermal occurrence of IL-1β, TNF-α and IL-23 were also significantly increased in the non-lesional HS epidermis but not in the dermis. On the contrary, no significant differences were detected regarding the dermal cellular components and Th1/Th17-related mediators. In summary, our results indicate KCs as crucial players in the first stages of HS development since all the investigated KC-derived molecules’ expression were increased even in non-lesional HS skin in contrast to the (adaptive) dermal components which showed similar levels in AGR and non-lesional HS skin but were prominently elevated in lesional HS skin in parallel with to the further enhancement of the innate immune components.