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Generalized pustular psoriasis (GPP) is considered to be a distinct clinical entity from psoriasis vulgaris (PV), with different clinical and histological manifestations. The pathogenesis of GPP has not been thoroughly elucidated, especially in those patients lacking interleukin (IL)36RN. In present study, we performed RNA sequence analysis on skin lesions from 10 GPP patients (4 with and 6 without IL36RN mutation) and 10 PV patients without IL36RN mutation. Compared with PV, significantly overexpressed genes in GPP patients were enriched in IL-17 signalling pathway (MMP1, MMP3, DEFB4A and DEFB4B, etc.) and associated with neutrophil infiltration (MMP1, MMP3, ANXA and SERPINB, etc.). GPP with IL36RN mutations evidenced WNT11 upregulation and IL36RN downregulation in comparison to those GPP without IL36RN mutations. The expression of IL-17A/IL-36 in skin or serum and the origin of IL-17A in skin were also investigated. IL-17A expression in skin was significantly higher in GPP than PV patients, whereas, there were no differences in skin IL-36α/IL-36γ/IL-36RA or serum IL-17A/IL-36α/IL-36γ between GPP than PV. Besides, double immunofluorescence staining of MPO/IL-17A or CD3/IL-17A further confirmed that the majority of IL-17A in GPP skin was derived from neutrophils, but not T cells. These data emphasized the role of neutrophil-derived IL-17A in the pathogenesis of GPP with or without IL36RN mutations. Targeting neutrophil-derived IL-17A might be a promising treatment for GPP., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Erythrodermic psoriasis (EP) is a severe and rare condition characterized by prominent erythema and scaling over 75 % of the body surface area. Unlike psoriasis vulgaris (PV), EP carries high risk of systemic involvement, including superficial skin infections and sepsis, particularly those caused by Staphylococcus aureus., Objective: To explore the microecological characteristics of EP and detect the levels of antimicrobial peptides (AMPs) in both skin and serum of EP patients., Methods: In this study, skin microbiomes of 10 EP patients were analyzed through 16S rRNA gene sequencing. The expressions of AMPs, Interleukin-4/13 (IL-4/13), Interleukin-17 (IL-17) and Interferon-γ (IFN-γ) in skin were detected via immunohistochemical staining and serum levels of AMP were evaluated by ELISA. We also enrolled 10 AD and 10 PV patients as controls., Results: EP patients retained rich microbial diversity, dominated by S. aureus. The AMPs of hBD2, LL-37, and RNase7 in EP keratinocytes were significantly lower than those in PV, but higher than those in AD. The expression levels of IL-4, IL-13 and IFN-γ in lesions are similar between EP and AD, but quite different from PV. What's more, the serum AMP levels in EP were similar to those in PV while significantly lower than in AD., Conclusion: We found EP patients have a rich microbial diversity dominated by S. aureus in lesions, while lower serum and skin AMPs expressions, which may account for the increased incidence of S. aureus cutaneous infections and sepsis in EP patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)