Wang Claire Q, Haxhinasto Sokol, Garcet Sandra, Kunjravia Norma, Cueto Inna, Gonzalez Juana, Rambhia Darshna, Harari Olivier, Sleeman Matthew A, Hamilton Jennifer D, Lim Wei Keat, Freudenberg Jan, Kalliolias George D, Thakker Paresh, Bissonnette Robert, Krueger James G
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
J Invest Dermatol. 2023 Jan;143(1):87-97.e14. doi: 10.1016/j.jid.2022.05.1094. Epub 2022 Aug 5.
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.
掌跖脓疱型银屑病（PPPP）和非脓疱型掌跖银屑病（NPPP）是局限性、使人衰弱的银屑病形式。PPPP和NPPP所涉及的炎症通路尚未完全了解。为了比较区分PPPP和NPPP的细胞和免疫学特征，共从30名患有PPPP、NPPP和寻常型银屑病（PV）的参与者以及10名健康参与者身上采集了皮肤活检样本。一部分参与者在停药3周后同意进行第二次活检。对皮损和非皮损皮肤的组织学染色显示，PPPP中的中性粒细胞计数高于NPPP和PV，NPPP中的CD8 T细胞计数更高。对皮肤活检样本进行RNA测序和转录分析显示，NPPP皮损中IFN-γ通路激活增强，但PPPP皮损皮肤中IL-17通路和中性粒细胞相关基因（如IL36A）的特征更强。在Olink平台上进行的血清分析检测到，NPPP中1型辅助性T细胞、IFN-γ诱导趋化因子的浓度更高，PPPP中中性粒细胞相关细胞因子的浓度更高。综上所述，这些证据表明，与PV和PPPP相比，NPPP中1型辅助性T细胞介导的炎症更明显，与PPPP相比，NPPP和PV中中性粒细胞相关活性更强。这些数据支持将与嗜中性粒细胞炎症相关的炎症通路（如IL-36信号传导）作为PPPP治疗开发的靶点。
