Primary alterations during the development of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin. OBJECTIVES: We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods. METHODS: Immune cell counts (T cells, dendritic cells, macrophages), Th1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL10, IL-23A, TGFB1, RORC, CCL20), keratinocyte-related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro-inflammatory molecules (IL1B, IL6, TNFA, IL-23A) were investigated in the three groups by RNASeq, RT-qPCR, immunohistochemistry and immunofluorescence. RESULTS: Epidermal changes were already detectable in non-lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL-1ß, TNF-α and IL-23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF-α and IL-1ß expression remained at high levels while AMPs and IL-23 increased even more compared with non-lesional skin. In the dermis of non-lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17-related mediators were significantly elevated. CONCLUSIONS: Our findings that non-lesional HS epidermal keratinocytes produce not only AMPs and IL-1ß but also high levels of TNF-α and IL-23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non-inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF-α and IL-23 appear also in non-lesional HS seems to prove these cytokines as excellent therapeutic targets.

Improvement of clinical and immunological parameters after allergen-specific immunotherapy in atopic dermatitis.

BACKGROUND: Allergen immunotherapy (AIT) is considered a curative treatment in some atopic diseases, but in AD contradictory clinical results exist and the action of AIT has not been elucidated. In the literature, there is no evidence for parallel investigations of permeability barrier, cutaneous and blood immune responses after AIT in AD. OBJECTIVES: The objective was to investigate immune parameters in the blood and skin and to detect clinical and barrier changes after AIT in AD. METHODS: Mild-to-moderate AD patients (n = 14) with concomitant allergic rhinitis to house dust mites were selected. All patients received topical treatment, while eight patients were randomly selected for adjuvant AIT also. At baseline and after 6 months, clinical, barrier and immunological investigations (serum and skin tests) were performed. In selected patients, biopsies from atopy patch tests (APTs) were analysed by immunohistochemistry for AD-relevant immune cells and mediators. RESULTS: In the adjuvant AIT group, clinical parameters and barrier functions improved significantly. Blood immune parameters displayed no significant changes. Post-AIT APT became negative in all patients in the AIT group, but remained positive in the non-AIT group. Cutaneous dendritic cell and T-cell recruitment decreased significantly after allergen challenge in the AIT group, but no significant changes in skin or serum immunoglobulin E levels or prick test (SPT) reactivity were detected. CONCLUSIONS: Allergen immunotherapy is a beneficial adjuvant treatment for sensitized AD patients. AIT improves not only clinical symptoms, but also permeability barrier functions. The effect of AIT on sensitization should be detected by APT, not by SPT.