Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Department of Dermatology, The University of Hong Kong Shenzhen Hospital, Shenzhen, China.
Front Immunol. 2023 Jul 27;14:1194088. doi: 10.3389/fimmu.2023.1194088. eCollection 2023.
Bullous pemphigoid (BP) is an autoimmune skin-blistering disease. Systemic corticosteroids remain the first line treatment for moderate-to-severe BP with the potential for severe adverse events. Dupilumab has emerged as an alternative option for BP patients.
We evaluated the efficiency and safety of dupilumab on BP treatment and explored a mode of drug action in depth.
A multicenter retrospective cohort included 20 BP patients who received dupilumab with or without systemic corticosteroid in dupilumab group, and 20 matched BP patients who received corticosteroid alone in conventional group. Serum samples were collected from 20 patients (10 from dupilumab group and 10 from conventional group) at baseline and week 4. Compared to systemic corticosteroid alone, dupilumab with or without systemic corticosteroid was similarly efficacious in clinical remission at week4 (complete remission plus partial remission: 100%) and week24 (complete remission plus partial remission:100%), but allowing significant decreases in the cumulative doses of corticosteroids with reducing the incidence of adverse events. However, dupilumab did not decrease BP180 antibody despite an obvious clinical improvement. Comparative plasma proteomic analysis performed before and after treatment in 3 BP patients from dupilumab group revealed that drug use was associated with 30 differentially expressed proteins, including 26 down-regulated and 4 up-regulated proteins. The former consisted of immune related proteins involved in T/B cell interactions (inducible T-cell co-stimulator ligand, ICOSL) and in the activation of eosinophils (PRG2), mast cells (S100A12), and complement (CR2). TARC and ICOSL levels correlated with BP severity in patients who received either dupilumab or conventional treatment.
Dupilumab has similar efficacy in treating BP as conventional drugs, by inhibiting the activities of many types of immune cells and complement, and regulating the interactions between T and B cells.
大疱性类天疱疮（BP）是一种自身免疫性皮肤水疱病。对于中重度 BP，全身皮质类固醇仍然是首选治疗方法，但存在严重不良反应的风险。度普利尤单抗已成为 BP 患者的另一种选择。
我们评估了度普利尤单抗治疗 BP 的疗效和安全性，并深入探讨了其作用模式。
一项多中心回顾性队列研究纳入了 20 例接受度普利尤单抗联合或不联合全身皮质类固醇治疗的 BP 患者（度普利尤单抗组），以及 20 例接受单纯皮质类固醇治疗的匹配 BP 患者（常规组）。在基线和第 4 周采集了 20 例患者（10 例来自度普利尤单抗组，10 例来自常规组）的血清样本。与单纯全身皮质类固醇治疗相比，度普利尤单抗联合或不联合全身皮质类固醇在第 4 周（完全缓解+部分缓解：100%）和第 24 周（完全缓解+部分缓解：100%）的临床缓解率上同样有效，但显著减少了皮质类固醇的累积剂量，同时降低了不良反应的发生率。然而，尽管临床症状明显改善，但度普利尤单抗并不能降低 BP180 抗体。对 3 例度普利尤单抗组患者治疗前后的血浆蛋白质组学比较分析显示，药物使用与 30 种差异表达蛋白相关，其中 26 种下调蛋白和 4 种上调蛋白。前者包括与 T/B 细胞相互作用（诱导性 T 细胞共刺激配体 ICOSL）和嗜酸性粒细胞（PRG2）、肥大细胞（S100A12）和补体（CR2）激活相关的免疫相关蛋白。在接受度普利尤单抗或常规治疗的患者中，TARC 和 ICOSL 水平与 BP 严重程度相关。
度普利尤单抗治疗 BP 的疗效与传统药物相似，通过抑制多种免疫细胞和补体的活性，调节 T 和 B 细胞的相互作用。
