Dudina M A, Dogadin S A, Savchenko A A, Belenyuk V D
Krasnoyarsk State Medical University; Krasnoyarsk regional clinical hospital.
Krasnoyarsk State Medical University; Federal Research Center «Krasnoyarsk Science Center» of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of medical problems of the North.
Probl Endokrinol (Mosk). 2021 Nov 9;67(6):39-49. doi: 10.14341/probl12812.
Effective control of autoimmune inflammation in Graves' disease determines necessity to study the T helper (Th) and cytotoxic T-lymphocytes dysfunction, as well as the level of regulatory T-cells (Treg) activation in patients with Graves' disease on thyrostatic medication, which will clarify the immunomodulatory effects of long-term thiamazole treatment serve as targets for more specific therapies.
To study the phenotypic composition of T-lymphocytes in the peripheral blood of patients with Graves' disease to assess the direction of immune response depending on thimazole-induced euthyroidism duration.
A single-center, cohort, continuous, open-label, controlled trial was conducted to assess the phenotypic composition of T-lymphocytes in peripheral blood in women with Graves' disease on long-term thiamazole treatment. The phenotypic composition of T-lymphocytes was determined by flow cytometry using direct immunofluorescence with conjugated FITC monoclonal antibodies depending on the duration of thimazole-induced euthyroidism of long-term thiamazole treatment.
The study included 135 women with Graves' disease, mean age 43.09±12.81 years, 120 (88.91%) with a relapse of the disease and 15 (11.09%) with newly diagnosed hyperthyroidism. An increase of activated CD3+CD4+CD25+ was found in patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months, respectively, Me=0.94 (0.48-1.45), p=0.020) and Me=0.95 (0.41-1.80), p=0.025), in control group - Me=0.12 (0.03-0.68). Compared to the control an increase of CD4+CD25+CD127Low (Treg) was found in patients with a duration of thimazole-induced euthyroidism 5-8 and 9-12 months. The content of Treg in peripheral blood in Graves' disease patients with a duration of thimazole-induced euthyroidism more than 12 months decreases, but remains elevated relative to the control.
In patients with Graves' disease with a duration of thimazole-induced euthyroidism 5-8 months and 9-12 months the level of Treg has been increased. The increase of activated Th (CD3+CD4+CD25+) persists independently of thimazole-induced euthyroidism. In patients with Graves' disease with a duration of thimazole-induced euthyroidism for more than 12 months, there is a compensatory increase in regulatory T-lymphocyte, and the total number of T-helpers is restored to the control.
有效控制格雷夫斯病中的自身免疫炎症决定了有必要研究甲状腺功能正常的格雷夫斯病患者中辅助性T（Th）细胞和细胞毒性T淋巴细胞功能障碍以及调节性T细胞（Treg）的激活水平，这将阐明长期甲巯咪唑治疗的免疫调节作用，为更特异性的治疗提供靶点。
研究格雷夫斯病患者外周血中T淋巴细胞的表型组成，以评估根据甲巯咪唑诱导的甲状腺功能正常持续时间的免疫反应方向。
进行了一项单中心、队列、连续、开放标签、对照试验，以评估长期接受甲巯咪唑治疗的格雷夫斯病女性外周血中T淋巴细胞的表型组成。根据长期甲巯咪唑治疗中甲巯咪唑诱导的甲状腺功能正常的持续时间，使用结合异硫氰酸荧光素（FITC）单克隆抗体的直接免疫荧光通过流式细胞术确定T淋巴细胞的表型组成。
该研究纳入了135例格雷夫斯病女性，平均年龄43.09±12.81岁，其中120例（88.91%）疾病复发，15例（11.09%）为新诊断的甲状腺功能亢进症。在甲巯咪唑诱导的甲状腺功能正常持续时间为5 - 8个月和9 - 12个月的格雷夫斯病患者中，分别发现活化的CD3 + CD4 + CD25 +增加，中位数（Me）=0.94（0.48 - 1.45），p = 0.020）和Me = 0.95（0.41 - 1.80），p = 0.025），对照组Me = 0.12（0.03 - 0.68）。与对照组相比，在甲巯咪唑诱导的甲状腺功能正常持续时间为5 - 8个月和9 - 12个月的患者中发现CD4 + CD25 + CD127Low（Treg）增加。甲巯咪唑诱导的甲状腺功能正常持续时间超过12个月的格雷夫斯病患者外周血中Treg含量降低，但相对于对照组仍升高。
在甲巯咪唑诱导的甲状腺功能正常持续时间为5 - 8个月和9 - 12个月的格雷夫斯病患者中，Treg水平升高。活化的Th（CD3 + CD4 + CD25 +）增加独立于甲巯咪唑诱导的甲状腺功能正常而持续存在。在甲巯咪唑诱导的甲状腺功能正常持续时间超过12个月的格雷夫斯病患者中，调节性T淋巴细胞有代偿性增加，且辅助性T细胞总数恢复至对照水平。
