{"title":"Soluble Immune Checkpoints Associated With Disease Activity and Treatment Response in GD and TED.","authors":"Qinglei Yin, Tianyi Zhu, Dalong Song, Sijie Fang, Huifang Zhou, Haixia Guan","doi":"10.1210/clinem/dgae763","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Soluble immune checkpoints play an important role in peripheral tolerance that has seldom been investigated in Graves' disease (GD) and thyroid eye disease (TED).</p><p><strong>Objective: </strong>The objective of this work is to examine the alteration of soluble immune checkpoints in GD and TED.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"1537-1549"},"PeriodicalIF":5.0000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Endocrinology & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1210/clinem/dgae763","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
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.