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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：特发性眼眶炎症（IOI）是一种非特异性眼眶炎症性疾病，在眼眶疾病中患病率第三高，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患者的TCR表达以及糖皮质激素反应。
方法：本研究共纳入19名受试者，分为特发性眼眶炎症组（IOI组，n=13）和健康对照组（HC组，n=6),并将IOI组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）基于对糖皮质激素治疗的有效性程度。使用5'RACE技术结合唯一标识符（UID）数字标签校正技术，对IOI患者和健康对照者的外周血单个核细胞进行高通量TCR测序。TCRCDR3区域多样性,共享模式，以及IOI和HC组之间的差异序列，并对IOI(EF)和IOI(IN)组进行分析。
结果：发现IOI组TCRCDR3的多样性明显低于HC组，V基因的使用频率在组间差异显著。IOI(EF)组患者TCRCDR3的多样性显著低于IOI(IN)组患者，V和J基因使用频率在IOI(EF)组和IOI(IN)组之间有显著差异。此外,我们发现所有IOI样本共有133个核苷酸序列,并从中筛选出两个表达较高的序列.
结论：我们的结果表明，IOI患者存在特异性T细胞的异常克隆扩增，TCR多样性可能对糖皮质激素治疗的IOI的预后有影响。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发病机制提供新的见解。诊断和治疗预测。
方法：本研究共纳入19名受试者，分为特发性眼眶炎症组（IOI组，n=13）和健康对照组（HC组，n=6),并将IOI组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）基于对糖皮质激素治疗的有效性程度。使用5'RACE技术结合唯一标识符（UID）数字标签校正技术，对IOI患者和健康对照者的外周血单个核细胞进行高通量TCR测序。TCRCDR3区域多样性,共享模式，以及IOI和HC组之间的差异序列，并对IOI(EF)和IOI(IN)组进行分析。
结果：发现IOI组TCRCDR3的多样性明显低于HC组，V基因的使用频率在组间差异显著。IOI(EF)组患者TCRCDR3的多样性显著低于IOI(IN)组患者，V和J基因使用频率在IOI(EF)组和IOI(IN)组之间有显著差异。此外,我们发现所有IOI样本共有133个核苷酸序列,并从中筛选出两个表达较高的序列.
结论：我们的结果表明，IOI患者存在特异性T细胞的异常克隆扩增，TCR多样性可能对糖皮质激素治疗的IOI的预后有影响。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发病机制提供新的见解。诊断和治疗预测。
