Molecular improvement of IL-23 inhibition revealed by single-cell RNA sequencing in concurrent psoriasis and systemic lupus erythematosus

Psoriasis and systemic lupus erythematosus (SLE) are chronic inflammatory diseases with rare coexistence, sharing the IL-23/IL-17 axis as a pathogenic pathway. A 42-year-old male with both conditions was successfully treated with the IL-23 inhibitor guselkumab, improving psoriasis without worsening SLE over 2.5 years. Single-cell RNA sequencing of skin biopsies revealed a decrease in T17 cells and IL-17-related transcripts post-treatment. Gene Set Enrichment Analysis showed reduced IFN-? and IFN-a responses, indicating broader inflammatory modulation. This study suggests IL-23 inhibitors may be a promising treatment for concurrent psoriasis and SLE, pending larger cohort validation. Overall design: Skin biopsy samples were collected from a patient with concurrent psoriasis and SLE, including non-lesional, pre-treatment lesional, and post-treatment lesional skin after 12 weeks of IL-23 inhibitor therapy. Single-cell RNA sequencing was performed to analyze gene expression, focusing on T-cell subsets and inflammatory pathways. Gene Set Enrichment Analysis was used to identify differentially regulated pathways, particularly IFN responses, pre- and post-treatment.

银屑病（Psoriasis）与系统性红斑狼疮（systemic lupus erythematosus, SLE）均为慢性炎症性疾病，二者合并发病较为罕见，且共享IL-23/IL-17轴作为核心致病通路。本研究纳入1例同时罹患两种疾病的42岁男性患者，经IL-23抑制剂古塞奇单抗（guselkumab）治疗后获得临床成功：在2.5年的随访周期内，患者银屑病症状得到显著改善，且未出现系统性红斑狼疮病情加重的情况。对患者皮肤活检样本开展单细胞RNA测序（single-cell RNA sequencing）分析后发现，治疗后T17细胞及IL-17相关转录本的表达水平均出现下调。基因集富集分析（Gene Set Enrichment Analysis）结果显示，干扰素-γ（IFN-γ）与干扰素-α（IFN-α）相关的免疫应答通路活性显著降低，提示该治疗方案具备更广泛的炎症调控效应。本研究表明，IL-23抑制剂或可为同时合并银屑病与系统性红斑狼疮的患者提供一种潜在治疗选择，相关结论仍需更大规模的队列研究加以验证。整体实验设计：从同时罹患银屑病与系统性红斑狼疮的患者体内采集皮肤活检样本，涵盖非皮损区皮肤、治疗前皮损区皮肤，以及接受IL-23抑制剂治疗12周后的治疗后皮损区皮肤样本。通过单细胞RNA测序分析基因表达特征，重点聚焦T细胞亚群与炎症信号通路。采用基因集富集分析对比治疗前后差异调控的通路，尤其是干扰素相关免疫应答通路。