Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom; Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Greater Manchester, United Kingdom.
Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom.
J Allergy Clin Immunol. 2024 May;153(5):1369-1380.e15. doi: 10.1016/j.jaci.2023.12.021. Epub 2024 Jan 4.
Solar urticaria is a rare photodermatosis characterized by rapid-onset sunlight-induced urticaria, but its pathophysiology is not well understood.
We sought to define cutaneous cellular and molecular events in the evolution of solar urticaria following its initiation by solar-simulated UV radiation (SSR) and compare with healthy controls (HC).
Cutaneous biopsy specimens were taken from unexposed skin and skin exposed to a single low (physiologic) dose of SSR at 30 minutes, 3 hours, and 24 hours after exposure in 6 patients with solar urticaria and 6 HC. Biopsy specimens were assessed by immunohistochemistry and bulk RNA-sequencing analysis.
In solar urticaria specimens, there was enrichment of several innate immune pathways, with striking early involvement of neutrophils, which was not observed in HC. Multiple proinflammatory cytokine and chemokine genes were upregulated (including IL20, IL6, and CXCL8) or identified as upstream regulators (including TNF, IL-1β, and IFN-γ). IgE and FcεRI were identified as upstream regulators, and phosphorylated signal transducer and activator of transcription 3 expression in mast cells was increased in solar urticaria at 30 minutes and 3 hours after SSR exposure, suggesting a mechanism of mast cell activation. Clinical resolution of solar urticaria by 24 hours mirrored resolution of inflammatory gene signature profiles. Comparison with available datasets of chronic spontaneous urticaria showed transcriptomic similarities relating to immune activation, but several transcripts were identified solely in solar urticaria, including CXCL8 and CSF2/3.
Solar urticaria is characterized by rapid signal transducer and activator of transcription 3 activation in mast cells and involvement of multiple chemotactic and innate inflammatory pathways, with FcεRI engagement indicated as an early event.
日光性荨麻疹是一种罕见的光皮病，其特征是迅速出现的阳光诱导性荨麻疹，但发病机制尚不清楚。
我们试图在日光性荨麻疹发病后，通过模拟太阳光的紫外线（SSR）照射来确定皮肤细胞和分子的变化，并与健康对照组（HC）进行比较。
在 6 例日光性荨麻疹患者和 6 例 HC 中，分别在暴露于 SSR 后 30 分钟、3 小时和 24 小时，取未暴露皮肤和单次低（生理）剂量 SSR 暴露皮肤的皮肤活检标本。通过免疫组织化学和批量 RNA 测序分析进行活检标本评估。
在日光性荨麻疹标本中，有几个先天免疫途径的富集，早期有明显的中性粒细胞参与，而在 HC 中则没有观察到。多个前炎症细胞因子和趋化因子基因被上调（包括 IL20、IL6 和 CXCL8）或被鉴定为上游调节因子（包括 TNF、IL-1β 和 IFN-γ）。IgE 和 FcεRI 被鉴定为上游调节因子，SSR 暴露后 30 分钟和 3 小时，日光性荨麻疹中肥大细胞的磷酸化信号转导和转录激活子 3 表达增加，提示肥大细胞激活的机制。24 小时后，日光性荨麻疹的临床缓解与炎症基因特征谱的缓解一致。与慢性自发性荨麻疹的可用数据集进行比较显示，与免疫激活有关的转录组相似，但在日光性荨麻疹中仅鉴定出几个转录本，包括 CXCL8 和 CSF2/3。
日光性荨麻疹的特征是肥大细胞中信号转导和转录激活子 3 的快速激活，涉及多种趋化和先天炎症途径，FcεRI 的参与被认为是早期事件。
