Comparison of the Inflammatory Circuits in Psoriasis Vulgaris, Non‒Pustular Palmoplantar Psoriasis, and Palmoplantar Pustular Psoriasis.

Autor: Wang CQ; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Haxhinasto S; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Garcet S; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Kunjravia N; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Cueto I; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Gonzalez J; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Rambhia D; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA., Harari O; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Sleeman MA; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Hamilton JD; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Lim WK; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Freudenberg J; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Kalliolias GD; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Thakker P; Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA., Bissonnette R; Innovaderm Research, Montreal, Canada., Krueger JG; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA. Electronic address: jgk@rockefeller.edu.
Jazyk: angličtina
Zdroj: The Journal of investigative dermatology [J Invest Dermatol] 2023 Jan; Vol. 143 (1), pp. 87-97.e14. Date of Electronic Publication: 2022 Aug 05.
DOI: 10.1016/j.jid.2022.05.1094
Abstrakt: Palmoplantar pustular psoriasis (PPPP) and non‒pustular palmoplantar psoriasis (NPPP) are localized, debilitating forms of psoriasis. The inflammatory circuits involved in PPPP and NPPP are not well-understood. To compare the cellular and immunological features that differentiate PPPP and NPPP, skin biopsies were collected from a total of 30 participants with PPPP, NPPP, and psoriasis vulgaris (PV) and from 10 healthy participants. A subset consented to a second biopsy after 3 additional weeks off medication. Histologic staining of lesional and nonlesional skin showed higher neutrophil counts in PPPP than in NPPP and PV and higher CD8 + T-cell counts in NPPP. RNA sequencing and transcriptional analysis of skin biopsies showed enhanced IFN-γ pathway activation in NPPP lesions but stronger signatures of IL-17 pathway and neutrophil-related genes (e.g., IL36A) in PPPP lesional skin. Serum analysis on the Olink platform detected higher concentrations of T helper type 1, IFN-γ‒inducible chemokines in NPPP, and higher neutrophil-associated cytokines in PPPP. Taken together, this evidence suggests more pronounced T helper 1‒mediated inflammation in NPPP than in PV and PPPP and stronger neutrophil-associated activity in PPPP than in NPPP and PV. These data support targeting inflammatory pathways associated with neutrophilic inflammation (e.g., IL-36 signaling) for therapeutic development in PPPP.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE