Department of Dermatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
J Dermatol. 2022 Sep;49(9):845-850. doi: 10.1111/1346-8138.16428. Epub 2022 May 10.
We report a patient with bullous pemphigoid (BP) who was successfully treated with dupilumab monotherapy. To clarify the underlying mechanism of this effective treatment, we investigated the dynamics of a variety of cytokine-producing T cells before and after treatment in the circulation and in blister fluid using flow cytometry. The patient was a 72-year-old woman who had a pruritic eruption consisting of erythema and tense blisters on the whole body. The skin biopsy and direct immunofluorescence of the skin were typical for BP. The serum level of anti-BP180NC16a antibodies was 111 U/ml. Flow cytometric analyses revealed that the proportions of circulating interleukin (IL)-4-, IL-13-, and IL-31-producing CD4 and CD8 T cells were substantially higher in our BP patient than in healthy subjects. Moreover, IL-4- and IL-13-producing CD4 and CD8 T cells were much higher in the blister fluids than in the circulation, whereas IL-31-producing CD4 and CD8 T cells were only slightly higher in the blister fluids. The proportions of circulating interferon (IFN)-γ-producing CD4 and CD8 T cells in the circulation were slightly lower in the patient than in healthy subjects. There was no significant difference in the circulating IL-17-producing CD4 and CD8 T cells between the patient and healthy subjects, although IL-17-producing CD4 and CD8 T cells were slightly higher in the blister fluids. Treatment with dupilumab promptly improved the pruritus and skin lesions, and anti-BP180 antibodies became negative. After treatment with dupilumab, the proportions of circulating IL-4- and IL-13-producing CD4 T cells mainly decreased and IL-17- and IL-31-producing CD4 T cells slightly decreased. There were no significant differences in the proportions of circulating IFN-γ-producing CD4 and CD8 T cells between before and after treatment. These results suggest that T-helper (Th)2 cells are involved in the pathogenesis of BP, and dupilumab exerts its effect mainly by suppressing Th2 cytokines.
我们报告了一例成功接受度普利尤单抗单药治疗的大疱性类天疱疮（BP）患者。为了阐明这种有效治疗的潜在机制，我们使用流式细胞术在循环和水疱液中研究了治疗前后各种细胞因子产生 T 细胞的动力学。患者为 72 岁女性，全身出现瘙痒性红斑和紧张性水疱。皮肤活检和皮肤直接免疫荧光检查均符合 BP 表现。血清抗 BP180NC16a 抗体水平为 111U/ml。流式细胞术分析显示，与健康受试者相比，我们的 BP 患者循环中 IL-4、IL-13 和 IL-31 产生的 CD4 和 CD8 T 细胞比例明显更高。此外，IL-4 和 IL-13 产生的 CD4 和 CD8 T 细胞在水疱液中明显高于循环中，而 IL-31 产生的 CD4 和 CD8 T 细胞仅略高于水疱液。与健康受试者相比，患者循环中 IFN-γ 产生的 CD4 和 CD8 T 细胞比例略低。患者与健康受试者之间循环中 IL-17 产生的 CD4 和 CD8 T 细胞无显著差异，尽管水疱液中 IL-17 产生的 CD4 和 CD8 T 细胞略高。度普利尤单抗治疗迅速改善了瘙痒和皮肤病变，抗 BP180 抗体转为阴性。度普利尤单抗治疗后，循环中 IL-4 和 IL-13 产生的 CD4 T 细胞比例主要降低，IL-17 和 IL-31 产生的 CD4 T 细胞略有降低。治疗前后循环中 IFN-γ 产生的 CD4 和 CD8 T 细胞比例无显著差异。这些结果表明，辅助性 T 细胞（Th）2 细胞参与 BP 的发病机制，度普利尤单抗主要通过抑制 Th2 细胞因子发挥作用。
