First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu-shi, 807-8555, Japan.
Sci Rep. 2022 Oct 7;12(1):16880. doi: 10.1038/s41598-022-19556-z.
Graves' disease (GD) is an organ-specific autoimmune disease, but there are a few studies that have evaluated how immunophenotypes are related to clinical symptoms and intractable pathology, or the effects of treatment on immunophenotypes. We performed peripheral blood immunophenotyping in GD. We assessed the proportion of functional subsets of T helper cells (such as Th1, Th17, Treg and Tfh cells), B cells (Naïve, IgM memory, Class-switched, IgDCD27 double negative and Plasmablasts cells), Monocytes, Dendritic cells and NK cells, and evaluated the relationship of immunophenotypes with clinical indices, disease activity, risk of relapse, and changes in immunophenotypes after treatment with antithyroid drugs. The activated Th17 cells, activated T follicular helper (Tfh) cells, and IgDCD27 double-negative B cells were higher in newly onset GD compared with healthy participants. Th17 cells were associated with thyroid autoantibodies, thyroid function, thyroid enlargement, and Graves' Recurrent Events After Therapy (GREAT) score; while double-negative B cells were associated with thyroid autoantibodies. Treatment with antithyroid drugs decreased the activated Tfh cells in parallel with the improvement in thyroid function. However, activated Th17 cells were not associated with clinical improvement and remained unchanged. Peripheral blood immunophenotyping identified the differential involvement of T and B cell subsets in the pathogenesis of GD. Abnormalities in the differentiation of Th17, Tfh, and double-negative B cells reflected the clinical pathology associated with autoantibody production and excess thyroid hormones. And Th17 cells are significantly associated with the marker for resistance to treatment. These results suggest the involvement of Th17 cell activation in the intractable pathology associated with potential immune abnormalities in GD. Clinical trial registration: #UMIN000017726 (Date: June 1st, 2015).
格雷夫斯病（GD）是一种器官特异性自身免疫性疾病，但有一些研究评估了免疫表型与临床症状和难治性病理的关系，或治疗对免疫表型的影响。我们对 GD 进行了外周血免疫表型分析。我们评估了 T 辅助细胞（如 Th1、Th17、Treg 和 Tfh 细胞）、B 细胞（Naïve、IgM 记忆、类别转换、IgDCD27 双阴性和浆母细胞）、单核细胞、树突状细胞和 NK 细胞的功能亚群比例，并评估了免疫表型与临床指标、疾病活动度、复发风险以及抗甲状腺药物治疗后免疫表型变化的关系。与健康参与者相比，新发 GD 患者的激活 Th17 细胞、激活滤泡辅助 T（Tfh）细胞和 IgDCD27 双阴性 B 细胞更高。Th17 细胞与甲状腺自身抗体、甲状腺功能、甲状腺肿大和治疗后格雷夫斯复发事件（GREAT）评分有关；而双阴性 B 细胞与甲状腺自身抗体有关。抗甲状腺药物治疗可降低激活的 Tfh 细胞，同时改善甲状腺功能。然而，激活的 Th17 细胞与临床改善无关，且保持不变。外周血免疫表型鉴定了 T 和 B 细胞亚群在 GD 发病机制中的差异参与。Th17、Tfh 和双阴性 B 细胞的分化异常反映了与自身抗体产生和过多甲状腺激素相关的临床病理学。Th17 细胞与治疗抵抗的标志物显著相关。这些结果表明，Th17 细胞的激活参与了与 GD 潜在免疫异常相关的难治性病理。临床试验注册号：#UMIN000017726（日期：2015 年 6 月 1 日）。
