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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Thyroid Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1364782
This article is part of the Research Topic Recent Advances in Thermal and Nonthermal Ablative Technologies of the Thyroid View all 8 articles

T-cell Exhaustion-related Genes in Graves' Disease: A Comprehensive Genome Mapping Analysis

Provisionally accepted
Zhengrong Jiang Zhengrong Jiang 1Huibin Huang Huibin Huang 1*Huiyao Cai Huiyao Cai 1Yizhao Lin Yizhao Lin 2Ruhai Lin Ruhai Lin 1Lijun Chen Lijun Chen 1
  • 1 The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
  • 2 Gutian County Hospital of Ningde City, ningde, China

The final, formatted version of the article will be published soon.

    Background: T-cell exhaustion (Tex) can be beneficial in autoimmune diseases, but its role in Graves' disease (GD), an autoimmune disorder of the thyroid, remains unknown. This study investigated Tex-related gene expression in GD patients to discern the potential contributions of these genes to GD pathogenesis and immune regulation.Methods: Through gene landscape analysis, a protein-protein interaction network of 40 Tex-related genes was constructed. mRNA expression levels were compared between GD patients and healthy control (HCs). Unsupervised clustering categorized GD cases into subtypes, revealing distinctions in gene expression, immune cell infiltration, and immune responses. Weighted gene co-expression network analysis and differential gene expression profiling identified potential therapeutic targets. RT-qPCR validation of candidate gene expression was performed using blood samples from 108 112 GD patients. Correlations between Tex-related gene expression and clinical indicators were analyzed.Results: Extensive Tex-related gene interactions were observed, with six genes displaying aberrant expression in GD patients. This was associated with atypical immune cell infiltration and regulation. Cluster analysis delineated two GD subtypes, revealing notable variations in gene expression and immune responses. Screening efforts identified diverse drug candidates for GD treatment. The Tex-related gene CBL was identified for further validation and showed reduced mRNA expression in GD patients, especially in cases of relapse. CBL mRNA expression was significantly lower in patients with moderate-to-severe thyroid enlargement than in those without such enlargement. Additionally, CBL mRNA expression was negatively correlated with the disease-specific indicator thyrotropin receptor antibodies.Conclusions: Tex-related genes modulate GD pathogenesis, and their grouping aids subtype differentiation and exploration of therapeutic targets. CBL represents a potential marker for GD recurrence.

    Keywords: Graves' disease, T-cell exhaustion, weighted gene co-expression network analysis, cbl, enlargement of thyroid gland

    Received: 03 Jan 2024; Accepted: 25 Jul 2024.

    Copyright: © 2024 Jiang, Huang, Cai, Lin, Lin and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Huibin Huang, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China

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