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- W3036280960 abstract "Hidradenitis Suppurativa is an autoinflammatory disorder of keratinization with a major inflammatory contribution from the Th17 axis. We have previously shown that in addition to previously described IL-17A & IL-17F; IL-17C is found at higher levels by both IHC and rt-PCR in lesional HS skin. We asked whether the IL-17 axis mediates disease activity by using an IL-17RA antagonist Brodalumab to examine histological and transcriptomic features of disease in 10 individuals with HS. Biopsies as per previously published consensus criteria were taken at Baseline and at Weeks 4 and 12 after treatment with an IL-17RA antagonist. Elevated levels keratinocyte derived genes (S100A9: logFCH =10.19; CXCL1: logFCH=5.46; CXCL8: logFCH=5.2), B-cell associated genes (IGHG3: logFCH=14.49) and cell trafficking chemokines (CXCl13: logFCH=7.62) were significantly elevated compared to normal site matched controls. IL-17RA antagonism resulted in statistically significant reductions in CXCL1, CXCL8, IL-36a to the level of unaffected HS patient tissue as confirmed by rt-PCR by Week 4. Histology demonstrates a significant reduction in CD11+ and CD3+ dermal cells (measured by quantitative IHC) by week 4 (p<0.01) continuing on to Week 12. Significant reductions in transepithelial neutrophil trafficking (measured by quantitative IHC) into dermal epithelialized tunnels was also noted. Morphological changes in epidermal psoriasiform hyperplasia were seen by Week 12 of therapy. Epidermal psoriasiform hyperplasia and trans-epithelial neutrophil migration in HS epidermis and epithelialized tunnels have parallels with Psoriasis Vulgaris and Generalized Pustular Psoriasis. IL17RA antagonism demonstrates rapid (by week 4) reduction in expression of B and T cell trafficking chemokines as measured by RT-PCR and significant alterations in epidermal morphology by Week 12. This highlights the role of IL-17 mediated feed-forward inflammation as in psoriasis and transepithelial neutrophil trafficking in dermal tunnels in HS." @default.
- W3036280960 created "2020-06-25" @default.
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- W3036280960 date "2020-07-01" @default.
- W3036280960 modified "2023-09-30" @default.
- W3036280960 title "880 Targeted IL-17RA antagonism ameliorates histological and transcriptomic features of hidradenitis suppurativa: A proof of concept study" @default.
- W3036280960 doi "https://doi.org/10.1016/j.jid.2020.03.896" @default.
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