Soluble Immune Checkpoints Associated With Disease Activity and Treatment Response in GD and TED.

IF 5 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Qinglei Yin, Tianyi Zhu, Dalong Song, Sijie Fang, Huifang Zhou, Haixia Guan
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引用次数: 0

Abstract

Context: Soluble immune checkpoints play an important role in peripheral tolerance that has seldom been investigated in Graves' disease (GD) and thyroid eye disease (TED).

Objective: The objective of this work is to examine the alteration of soluble immune checkpoints in GD and TED.

Methods: We performed a quantitative multiplex analysis of 17 immune checkpoint proteins in serum from 50 GD patients without TED, 28 GD patients with TED, and 40 healthy controls. The association with demographic, serologic, clinical features and 27 cytokines was analyzed. A follow-up was conducted in GD patients without TED. Functional outcomes of sLAG-3 and sGITR were assessed in cell cultures using rh-LAG3, rh-GITR, an antagonistic LAG-3 antibody, and an antagonistic GITR antibody.

Results: GD Patients with TED had distinct sICP and cytokine profiles compared with GD patients without TED. Active patients with TED exhibited elevation in the levels of sBTLA, sLAG-3, sGITR, sCD80, sCD86, and sPD-L1. Further, GD patients without TED with high sBTLA, sCD27, and sCD40 levels at baseline showed a better improvement in thyrotropin receptor antibody titers after antithyroid drug treatment. Adding recombinant human GITR and LAG-3 to peripheral blood mononuclear cell cultures resulted in increased inflammatory cytokine secretion and decreased anti-inflammatory cytokine secretion.

Conclusion: The present study uncovers disturbed soluble immune checkpoints and cytokines in GD patients with and without TED and may pave the way for novel immunological screening, allowing for identification of patients with TED at higher risk of developing active disease and patients with GD a better treatment response after antithyroid drug treatment.

与 GD 和 TED 疾病活动和治疗反应相关的可溶性免疫检查点。
背景:可溶性免疫检查点在外周耐受性中发挥着重要作用,但在巴塞杜氏病(GD)和甲状腺眼病(TED)中却鲜有研究:这项工作的目的是研究可溶性免疫检查点在 GD 和 TED 中的变化:我们对50名未患TED的GD患者、28名患TED的GD患者和40名健康对照者血清中的17种免疫检查点蛋白进行了多重定量分析。分析了其与人口统计学、血清学、临床特征和 27 种细胞因子的关系。对无 TED 的 GD 患者进行了随访。使用 rh-LAG3、rh-GITR、拮抗 LAG-3 的抗体和拮抗 GITR 的抗体在细胞培养物中评估了 sLAG-3 和 sGITR 的功能结果:结果:与无 TED 的 GD 患者相比,有 TED 的 GD 患者的 sICP 和细胞因子特征截然不同。活动性 TED 患者的 sBTLA、sLAG-3、sGITR、sCD80、sCD86 和 sPD-L1 水平升高。此外,sBTLA、sCD27 和 sCD40 水平基线较高的非 TED 广东籍患者在接受抗甲状腺药物(ATD)治疗后,甲状腺素受体抗体(TRAb)滴度有较好的改善。在PBMC培养物中加入重组人GITR和LAG-3会导致炎性细胞因子分泌增加,而抗炎细胞因子分泌减少:本研究揭示了有TED和无TED的GD患者体内受干扰的可溶性免疫检查点和细胞因子,为新型免疫学筛查铺平了道路,可用于识别有更高风险发展为活动性疾病的TED患者和经ATD治疗后有更好治疗反应的GD患者。
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来源期刊
Journal of Clinical Endocrinology & Metabolism
Journal of Clinical Endocrinology & Metabolism 医学-内分泌学与代谢
CiteScore
11.40
自引率
5.20%
发文量
673
审稿时长
1 months
期刊介绍: The Journal of Clinical Endocrinology & Metabolism is the world"s leading peer-reviewed journal for endocrine clinical research and cutting edge clinical practice reviews. Each issue provides the latest in-depth coverage of new developments enhancing our understanding, diagnosis and treatment of endocrine and metabolic disorders. Regular features of special interest to endocrine consultants include clinical trials, clinical reviews, clinical practice guidelines, case seminars, and controversies in clinical endocrinology, as well as original reports of the most important advances in patient-oriented endocrine and metabolic research. According to the latest Thomson Reuters Journal Citation Report, JCE&M articles were cited 64,185 times in 2008.
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