Department of Dermatology, Saitama Medical University, Saitama Medical Center, Saitama, Japan.
Dermatology. 2017;233(2-3):242-249. doi: 10.1159/000475546. Epub 2017 Jun 10.
Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is characterized by severe drug-induced reactions with extensive cutaneous lesions and visceral involvement. Although T cell-mediated hypersensitivity reactions to drugs may be involved in the pathogenesis of DRESS, there is limited data regarding the T-cell phenotypes responsible for the pathogenesis of DRESS.
Using flow cytometry, we investigated the cytokine profiles and cutaneous lymphocyte antigen (CLA) expression in circulating T cells in patients with DRESS.
The proportions of circulating IL-4- and IL-13-producing CD4+ T cells, but not CD8+ T cells, were significantly higher in patients with DRESS during the active stage of the disease than in healthy subjects, and these proportions declined during the recovery stage. No differences in the proportions of circulating IFN-γ-, IL-17-, and IL-22-producing CD4+ and CD8+ T cells were observed between patients with DRESS and healthy subjects. A strong correlation between the proportion of IL-13-producing CD4+ T cells and serum levels of thymus and activation-regulated chemokine was observed. The proportion of CLA-expressing CD4+ T cells was significantly higher during the active stage of the disease. Moreover, the proportion of IL-13-producing CD4+ T cells was higher in the CLA+ subset than in the CLA- subset.
Skin-homing IL-13-producing CD4+ T cells may be involved in the pathogenesis of DRESS.
药物疹伴嗜酸性粒细胞增多和全身症状(DRESS),又称药物诱导的超敏反应综合征,其特征为广泛皮肤损伤和内脏受累的严重药物诱导反应。虽然药物诱导的 T 细胞超敏反应可能参与 DRESS 的发病机制,但关于导致 DRESS 发病机制的 T 细胞表型的数据有限。
使用流式细胞术,我们研究了 DRESS 患者循环 T 细胞中的细胞因子谱和皮肤淋巴细胞抗原(CLA)表达。
与健康受试者相比,DRESS 患者疾病活动期循环中产生 IL-4 和 IL-13 的 CD4+T 细胞的比例显著升高,而 CD8+T 细胞的比例没有升高,且在恢复期下降。DRESS 患者与健康受试者之间循环中产生 IFN-γ、IL-17 和 IL-22 的 CD4+和 CD8+T 细胞的比例没有差异。产生 IL-13 的 CD4+T 细胞的比例与血清胸腺激活调节趋化因子水平之间存在很强的相关性。疾病活动期 CLA 表达的 CD4+T 细胞的比例明显更高。此外,产生 IL-13 的 CD4+T 细胞在 CLA+亚群中的比例高于 CLA-亚群。
皮肤归巢的 IL-13 产生的 CD4+T 细胞可能参与 DRESS 的发病机制。