文章：

免疫相关性大疱性类天疱疮中白细胞介素-4与-13基因表达谱提示IL-4/IL-13抑制剂疗效

Interleukin-4 and -13 Gene Expression Profiles in Immune-Related Bullous Pemphigoid Indicate Efficacy of IL-4/IL-13 Inhibitors

原文发布日期：31 May 2025

DOI: 10.3390/cancers17111845

类型: Article

开放获取: 是

英文摘要：

Background/Objectives:Cutaneous side effects are the most common immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) and affect 70–90% of patients. Besides diverse types of exanthema, rare skin toxicity includes bullous dermatoses in 0.3% of cases. Systemic steroids are the first-line treatment for immune-related bullous pemphigoid (irBP); however, some cases are corticosteroid-resistant. IrBP is one of the irAEs most frequently chronic and associated with long-term steroid use. However, steroids may interfere with tumor response. Therefore, alternative treatment strategies for irBP are desperately needed. Dupilumab, a monoclonal antibody blocking the receptor binding of interleukin-4 (IL-4) and interleukin-13 (IL-13), has been successfully used to treat spontaneous forms of bullous pemphigoid (BP). In this study, we analyzed the gene expression profiles of BP and irBP.Patients and Methods:A retrospective multicenter study evaluated the gene expression profiles of irBP and BP in comparison to healthy controls. Gene expression analyses of skin biopsies were performed using NanoString technology from patients with BP (n = 17), irBP (n = 19), and healthy skin (n = 24) after the patients had consented to participate in this study, and differentially expressed genes (DEGs) were determined using Rosalind software.Results:Compared to healthy skin, BP showed 167 DEGs, and irBP revealed 99 DEGs. Some of the DEGs from irBP and BP vs. healthy skin overlapped. Specifically, IL-4- and IL-13-associated genes were upregulated in both irBP and BP compared to healthy skin. Interestingly, expression profiles of BP vs. irBP also showed 13 DEGs.Conclusions:These findings suggest a possibility for therapeutic efficacy of IL-4 and IL-13 inhibitors in the treatment of irBP.

摘要翻译： 

背景/目的：皮肤副作用是免疫检查点抑制剂（ICIs）引起的最常见免疫相关不良事件（irAEs），影响70-90%的患者。除多种类型的皮疹外，罕见的皮肤毒性包括0.3%的病例出现大疱性皮肤病。系统性类固醇是免疫相关大疱性类天疱疮（irBP）的一线治疗；然而，部分病例对皮质类固醇耐药。irBP是最常慢性化且与长期使用类固醇相关的irAEs之一。但类固醇可能干扰肿瘤应答。因此，迫切需要针对irBP的替代治疗策略。度普利尤单抗是一种阻断白细胞介素-4（IL-4）和白细胞介素-13（IL-13）受体结合的单克隆抗体，已成功用于治疗自发性大疱性类天疱疮（BP）。本研究分析了BP与irBP的基因表达谱。 患者与方法：一项回顾性多中心研究评估了irBP和BP相较于健康对照的基因表达谱。在患者同意参与本研究后，使用NanoString技术对BP（n=17）、irBP（n=19）和健康皮肤（n=24）患者的皮肤活检组织进行基因表达分析，并采用Rosalind软件确定差异表达基因（DEGs）。 结果：与健康皮肤相比，BP显示167个DEGs，irBP显示99个DEGs。irBP和BP相较于健康皮肤的部分DEGs存在重叠。具体而言，与健康皮肤相比，irBP和BP中IL-4和IL-13相关基因均上调。值得注意的是，BP与irBP的表达谱比较也显示出13个DEGs。 结论：这些发现提示IL-4和IL-13抑制剂在治疗irBP中可能具有疗效。

原文链接：

Interleukin-4 and -13 Gene Expression Profiles in Immune-Related Bullous Pemphigoid Indicate Efficacy of IL-4/IL-13 Inhibitors