Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Cytokine. 2018 Oct;110:416-419. doi: 10.1016/j.cyto.2018.05.009. Epub 2018 May 31.
IgG4-related disease (IgG4-RD) is a systemic disorder characterized by elevated serum IgG4 level, which is mediated by T follicular helper 2 (Tfh2) cell. However, the cytokines responsible for enhancing IgG4 production remain unclear in IgG4-RD. The aim of this study was to identify responsible Tfh2-related cytokines (interleukin (IL)-4 and IL-21) for enhancing IgG4 production in IgG4-RD. Peripheral blood mononuclear cells obtained from consecutive patients with active, untreated IgG4-RD and healthy controls were examined. The production of both IgG and IgG4 were significantly increased by stimulation with IL-4 alone as well as IL-21 alone compared to background stimulation with anti-CD40 antibody in IgG4-RD. On the other hand, the IgG4/IgG ratio was statistically higher by stimulation with IL-4 alone compared to the other Tfh2-related cytokines including IL-21 in IgG4-RD. IgG4 production was not increased by stimulation with IL-4 in healthy controls. These results suggest that IL-4 can contribute to the shift of balance of IgG subclasses toward IgG4 compared to the other Tfh2-related cytokines in IgG4-RD.
IgG4 相关疾病（IgG4-RD）是一种以血清 IgG4 水平升高为特征的系统性疾病，其由滤泡辅助性 T 细胞 2（Tfh2）细胞介导。然而，在 IgG4-RD 中，增强 IgG4 产生的细胞因子仍不清楚。本研究旨在鉴定与 Tfh2 相关的细胞因子（白细胞介素（IL）-4 和 IL-21），以确定其在 IgG4-RD 中增强 IgG4 产生的作用。检测了连续就诊的活动期、未经治疗的 IgG4-RD 患者和健康对照者的外周血单个核细胞。与 IgG4-RD 中抗 CD40 抗体的背景刺激相比，IL-4 单独刺激以及 IL-21 单独刺激均可显著增加 IgG 和 IgG4 的产生。另一方面，与包括 IL-21 在内的其他 Tfh2 相关细胞因子相比，IL-4 单独刺激时 IgG4/IgG 比值在统计学上更高。在健康对照者中，IL-4 刺激不会增加 IgG4 的产生。这些结果表明，与其他 Tfh2 相关细胞因子相比，IL-4 可促进 IgG4 亚类向 IgG4 平衡的转变。
