Wang Yifei, Zhang Xin, Teng Yun Te, Shen Chen
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Dermatology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Front Immunol. 2024 Dec 13;15:1499868. doi: 10.3389/fimmu.2024.1499868. eCollection 2024.
Bullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients' quality of life. Despite the widespread attention these two diseases have garnered within the dermatological field, the specific pathogenesis, particularly the molecular mechanisms underlying the pruritus, remains largely unclear. Limited clinical sequencing studies focusing on BP and PN have hindered the identification of pathological mechanisms and the exploration of effective treatment strategies.
To address this gap, we collected a total of 23 peripheral blood mononuclear cell samples from BP and PN patients, as well as healthy controls, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the shared immune regulatory networks and pruritus-related mechanisms between BP and PN.
Our study identified 161 differentially expressed genes shared between BP and PN, which were primarily enriched in immune activation and neural pathways, providing crucial molecular insights into the pruritus-related mechanisms of both diseases. Furthermore, using the machine learning algorithms of support vector machines and random forest, we pinpoint 7 crucial genes shared between the BP and PN databases. Among these, IL-27 emerged as a potential pivotal gene, as its mRNA expression levels strongly correlated with clinical parameters including pruritus scores, immunoglobulin E levels, and eosinophil counts. Validation experiments conducted on clinical samples from an additional 22 participants confirmed the upregulation of IL-27 expression in both BP and PN lesions.
This study is the first to unveil the shared inflammatory and immune pathways common to BP and PN, highlighting the critical role of IL-27 in the pathogenesis of these conditions. Our findings not only enhance the understanding of the intricate relationship between BP and PN, but also provide a foundation for the development of novel therapeutic strategies targeting these two dermatological conditions.
大疱性类天疱疮（BP）和结节性痒疹（PN）是慢性瘙痒性皮肤病，严重影响患者的生活质量。尽管这两种疾病在皮肤科领域受到了广泛关注，但其具体发病机制，尤其是瘙痒背后的分子机制，在很大程度上仍不清楚。针对BP和PN的临床测序研究有限，阻碍了病理机制的识别和有效治疗策略的探索。
为了填补这一空白，我们总共收集了23份来自BP和PN患者以及健康对照的外周血单个核细胞样本，并进行了RNA测序分析。通过整合生物信息学和机器学习技术，我们旨在揭示BP和PN之间共享的免疫调节网络和瘙痒相关机制。
我们的研究确定了BP和PN之间共有的161个差异表达基因，这些基因主要富集于免疫激活和神经通路，为这两种疾病的瘙痒相关机制提供了关键的分子见解。此外，使用支持向量机和随机森林的机器学习算法，我们在BP和PN数据库之间确定了7个关键基因。其中，IL-27成为一个潜在的关键基因，因为其mRNA表达水平与包括瘙痒评分、免疫球蛋白E水平和嗜酸性粒细胞计数在内的临床参数密切相关。对另外22名参与者的临床样本进行的验证实验证实了BP和PN皮损中IL-27表达的上调。
本研究首次揭示了BP和PN共有的炎症和免疫通路，突出了IL-27在这些疾病发病机制中的关键作用。我们的发现不仅增进了对BP和PN之间复杂关系的理解，也为针对这两种皮肤病的新型治疗策略的开发提供了基础。
