Composition and diversity analysis of the TCR CDR3 repertoire in patients with idiopathic orbital inflammation using high-throughput sequencing.
Composition and diversity analysis of the TCR CDR3 repertoire in patients with idiopathic orbital inflammation using high-throughput sequencing.
复制标题
使用高通量测序的特发性轨道炎症患者中TCR CDR3库的组成和多样性分析。
DOI：
10.1186/s12886-023-03248-x
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发表时间：
2023-12-04
影响因子：
2
通讯作者：
中科院分区：
文献类型：
--
作者：
特发性眼眶炎症（IOI）是一种非特异性眼眶炎症性疾病，在眼眶疾病中发病率排名第三，其发病机制与T细胞介导的免疫反应有关。本研究旨在通过高通量测序研究 IOI 患者和健康受试者之间 T 细胞受体 (TCR) 表达的差异，并表征 IOI 患者中 TCR 表达以及糖皮质激素反应的特征。本研究共纳入19例受试者，分为特发性眼眶炎症组（IOI组，n = 13）和健康对照组（HC组，n = 6），IOI组内进一步分为糖皮质激素治疗敏感组（IOI（EF）组，n = 6）和糖皮质激素治疗无效组（IOI（IN）组，n = 7）基于糖皮质激素治疗的有效性程度。采用5'RACE技术结合唯一标识符（UID）数字标签校正技术，对IOI患者和健康对照个体的外周血单个核细胞进行高通量TCR测序。分析了IOI和HC组之间以及IOI(EF)和IOI(IN)组之间的TCR CDR3区域多样性、共享模式和差异序列。结果发现，IOI组TCR CDR3多样性显着低于HC组，且V基因使用频率组间差异显着。 IOI(EF)组患者TCR CDR3多样性显着低于IOI(IN)组患者，且V和J基因使用频率在IOI(EF)组和IOI(IN)组之间存在显着差异。此外，我们还发现了所有IOI样本中共有的133个核苷酸序列，并从中筛选出两条表达量较高的序列。我们的结果表明，IOI 患者中存在特定 T 细胞的异常克隆扩增，并且 TCR 多样性可能对糖皮质激素治疗的 IOI 的预后产生影响。这项研究可能有助于更好地了解 IOI 的免疫状态，并为 T 细胞相关的 IOI 发病机制、诊断和治疗预测提供新的见解。在线版本包含可在 10.1186/s12886-023-03248-x 获取的补充材料。
Idiopathic orbital inflammation (IOI) is a nonspecific orbital inflammatory disease with the third highest prevalence among orbital diseases, and its pathogenesis is associated with T-cell-mediated immune responses. This study aimed to investigate the differences in T-cell receptor (TCR) expression between IOI patients and healthy subjects by high-throughput sequencing and to characterize TCR expression in patients with IOI and with respect to glucocorticoid response. A total of 19 subjects were enrolled in this study and were divided into the idiopathic orbital inflammation group (IOI group, n = 13) and the healthy control group (HC group, n = 6), and within the IOI group were further divided into the glucocorticoid therapy sensitive group (IOI(EF) group, n = 6) and the glucocorticoid therapy ineffective group (IOI(IN) group, n = 7) based on the degree of effectiveness to glucocorticoid therapy. High-throughput TCR sequencing was performed on peripheral blood mononuclear cells of IOI patients and healthy control individuals using 5’ RACE technology combined with Unique Identifier (UID) digital tag correction technology. The TCR CDR3 region diversity, sharing patterns, and differential sequences between the IOI and HC groups, and between the IOI(EF) and IOI(IN) groups were analyzed. It was found that the diversity of TCR CDR3 in the IOI group was significantly lower than that in the HC group, and the frequency of V gene use was significantly different between groups. The diversity of TCR CDR3 in patients in the IOI(EF) group was significantly lower than that in patients in the IOI(IN) group, and the frequency of V and J gene use was significantly different between the IOI(EF) group and the IOI(IN) group. Additionally, we found 133 nucleotide sequences shared in all IOI samples and screened two sequences with higher expression from them. Our results suggested that abnormal clonal expansion of specific T-cells exists in IOI patients and that TCR diversity may had an impact on the prognosis of glucocorticoid-treated IOI. This study may contribute to a better understanding of the immune status of IOI and provide new insights for T-cell -associated IOI pathogenesis, diagnosis and treatment prediction. The online version contains supplementary material available at 10.1186/s12886-023-03248-x.
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12.3
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