Background: Graves' disease (GD) is characterized by the production of autoantibodies against the TSHR (TRAbs). With long-term treatment, serum concentrations of TRAbs decline but in some patients, despite being clinically stable, TRAbs persist for many years.Objective: To investigate whether GD patients with persistence of TRAbs constitute a subset of patients that could be identified by phenotypic analysis of circulating lymphocytes, suggesting disease heterogeneity.Materials and methods: Peripheral blood lymphocytes (including naïve, memory and effector T and B cells, Th17, regulatory T cells (Treg), recent thymic emigrants (RTEs) and double positive CD4+CD8+ (DP) cells) were analysed by flow cytometry in a cross-sectional study in 25 clinically stable GD patients, five patients at onset of GD disease and 40 healthy donors (HDs).Results: GD patients with persistence of TRAbs showed a lower percentage of Treg and lower absolute numbers of central and effector memory CD8+ T cells than HD. No differences in RTEs were found in peripheral blood from GD patients compared to HD. Stable GD patients had higher percentage of DP cells of effector phenotype than HD.Conclusions: Using extensive phenotypic analysis of lymphocyte subpopulations, it is possible to detect changes that help to identify patients with persistent TSHR antibodies and may contribute to understand why the autoimmune response is maintained.

中文翻译：

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抗TSHR自身抗体持续存在于格雷夫斯病中外周淋巴细胞亚群的独特模式。

背景：格雷夫斯病（GD）的特征是产生针对TSHR（TRAbs）的自身抗体。经过长期治疗，TRAbs的血清浓度会下降，但即使在某些患者中，即使临床上稳定，TRAbs仍会持续多年。材料和方法：外周血淋巴细胞（包括幼稚，记忆和效应T细胞和B细胞，Th17，调节性T细胞（Treg），近期胸腺移出物（RTE）和双阳性CD4 + CD8 +（DP）通过流式细胞仪在25例临床稳定的GD患者，5例GD疾病发作的患者和40例健康供体（HD）的横断面研究中对细胞进行了分析。伴有TRAbs的GD患者比HD患者显示出较低的Treg百分比，中枢和效应记忆CD8 + T细胞的绝对数量也较低。与HD相比，GD患者的外周血RTE没有差异。稳定的GD患者具有比HD高的效应表型DP细胞百分比。结论：通过对淋巴细胞亚群的广泛表型分析，可以检测有助于识别具有持久TSHR抗体的患者的变化，并可能有助于理解为什么自身免疫反应是保持。