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甲状腺眼病患者免疫抑制治疗中血清PD-1调节及CD4+Foxp3+调节性T细胞的PD-1表达

Serum PD-1 regulation and PD-1 expression of CD4+Foxp3+ regulatory T cells in patients in thyroid eye disease associated with immunosuppression treatment.

作者信息

Sakai Atsushi, Tagami Mizuki, Misawa Norihiko, Haruna Yusuke, Tomita Mami, Honda Shigeru

机构信息

Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.

出版信息

Front Ophthalmol (Lausanne). 2024 Dec 16;4:1491053. doi: 10.3389/fopht.2024.1491053. eCollection 2024.

Abstract

PURPOSE

Thyroid eye disease (TED) primarily occurs in hyperthyroid patients, sometimes resulting in poor visual prognosis. Although other autoimmune diseases have been reported to be associated with serum programmed cell death 1 (PD-1), the relationship with TED remains unknown. This study investigated the relationship between TED and immune checkpoint molecules.

METHODS

Serum immune checkpoint molecules were measured in TED and control patient blood samples. In TED patients, blood samples were compared before and 6 months after steroid pulse treatment. Cytometry analysis was additionally performed in TED and control patients to compare the expression of (PD-1) of T cells.

RESULTS

Serum concentrations of PD-1 in TED and control patients were 163.49 ± 79.01 (pg/mL) and 123.58 ± 46.61 (pg/mL) ( = 0.03). Serum PD-L1 concentration in TED was 157.89 ± 55.34 (pg/mL), while 152.58 ± 22.70 (pg/mL) in control patients ( = 0.92). For flow cytometry analysis, the mean fluorescence intensity (MFI) ratio of PD-1 in Foxp3high CD45RA- of the CD4+ T cells and CD127-CD25high of the CD4+ T cells were higher in TED versus control patients ( = 0.04, = 0.02). There was also a higher percentage of PD-1 expressions on CD4+ T cells and Foxp3high CD45- T cells in TED patients versus that for control patients ( < 0.001, = 0.003).

CONCLUSIONS

PD-1 expression of CD4+Foxp3+ regulatory T cells appear to be associated with TED pathogenesis before and after treatment. Regulatory T cells expressed PD-1 have possibilities of clinical activity and autoimmune pathology of TED.

摘要

目的

甲状腺眼病(TED)主要发生于甲状腺功能亢进患者,有时会导致不良的视觉预后。尽管有报道称其他自身免疫性疾病与血清程序性细胞死亡1(PD-1)有关,但与TED的关系仍不清楚。本研究调查了TED与免疫检查点分子之间的关系。

方法

检测TED患者和对照患者血样中的血清免疫检查点分子。在TED患者中,比较类固醇脉冲治疗前后的血样。另外,对TED患者和对照患者进行细胞计数分析,以比较T细胞中(PD-1)的表达。

结果

TED患者和对照患者血清中PD-1浓度分别为163.49±79.01(pg/mL)和123.58±46.61(pg/mL)(P = 0.03)。TED患者血清PD-L1浓度为157.89±55.34(pg/mL),对照患者为152.58±22.70(pg/mL)(P = 0.92)。流式细胞术分析显示,与对照患者相比,TED患者CD4+ T细胞中Foxp3高表达CD45RA-的PD-1平均荧光强度(MFI)比值以及CD4+ T细胞中CD127-CD25高表达的PD-1 MFI比值更高(P = 0.04,P = 0.02)。TED患者CD4+ T细胞和Foxp3高表达CD45- T细胞上PD-1表达的百分比也高于对照患者(P < 0.001,P = 0.003)。

结论

CD4+Foxp3+调节性T细胞的PD-1表达似乎与TED治疗前后的发病机制有关。表达PD-1的调节性T细胞可能参与TED的临床活动和自身免疫病理过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97a1/11683052/4afda1eb530b/fopht-04-1491053-g001.jpg

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