注射用甲泼尼龙琥珀酸钠静脉冲击治疗Graves眼病对T细胞受体的影响

Effect of methylamytosaurus intravenous shock therapy on T cell receptor of Graves ophthalmopathy

目的通过对注射用甲泼尼龙琥珀酸钠静脉冲击治疗前后的Graves眼病(TAO)患者T细胞受体(TCR)进行测序,进一步探索注射用甲泼尼龙琥珀酸钠静脉冲击治疗TAO的免疫学机制,为新兴免疫学治疗提供理论依据。方法收集6例TAO患者,于诊断时、第1次冲击治疗结束时和第3次冲击治疗结束时的3个时间点采集外周血。提取外周血单个核细胞并提取RNA进行TCR免疫组库测序,后续进行高通量测序数据挖掘分析。结果3次激素冲击结束后,病情好转的TAO患者,其TCR多样性指数、VJ家族迁移、VJ家族频率变化差异无统计学意义。相反病情恶化的TAO患者,其高频VJ家族出现克隆扩增。TAO患者缓解伴随着Th17细胞的下降。结论注射用甲泼尼龙琥珀酸钠静脉冲击治疗TAO的机制是机体免疫平衡的重新建立,而不是自身反应性克隆的消除。

Objective To sequence the T cell receptor(TCR)of patients with Graves ophthalmopathy(TAO)before and after the treatment of intravenous injection of methylprednisolone,and to further explore the immunologic mechanism of the treatment of Tao by intravenous injection of methylprednisolone,so as to provide theoretical basis for the new immunologic treatment.Methods Six patients with TAO were collected from the outpatient department of the First Affiliated Hospital of Xi?an Jiaotong University.The peripheral blood was collected at three time points of diagnosis,the end of the first shock treatment and the end of the third shock treatment.The peripheral blood mononuclear cells(PBMCs)were extracted and RNA was extracted for TCR immunohistochemistry library sequencing,followed by high-throughput sequencing data mining analysis.Results After three hormone shocks,there was no significant difference in TCR diversity index,VJ family migration and VJ family frequency among the improved TAO patients.Conversely,the high frequency VJ family showed clonal expansion in worsening TAO patients.TAO remission was linked with the decrease of Th17 cells.Conclusion The mechanism of intravenous shock therapy of TAO by methylprednisolone is the reestablishment of immune balance rather than the elimination of autoreactive cloning.