Graves病和Graves眼病患者T细胞受体谱系研究

T cell receptor analysis in patients with Graves′disease and Graves′ophthalmopathy

目的通过对Graves病(Graves′disease,GD)和Graves眼病(thyroid associated ophthalmopathy,TAO)患者的T细胞受体(T cell receptor,TCR)测序,鉴定GD和TAO特异性TCR家族,为临床早期精确诊断提供依据。方法于西安交通大学第一附属医院门诊收集9例GD和6例TAO患者。对GD和TAO患者于诊断时采集外周血。收集20例与患者年龄和性别相匹配的健康对照外周血。分离外周血单个核细胞并提取RNA进行TCR免疫组库测序,并进行后续高通量数据挖掘分析。结果GD和TAO患者TCR多样性显著低于健康对照。挖掘TCR高通量测序数据,可分别构建GD和TAO两种疾病的特征性TCR数据库,分别包含157和116个VJ家族。这些VJ家族中存在两种疾病共有的家族,也存在两种疾病各自特有的家族。结论GD和TAO存在共同的发病基础,但是在某种程度上还是拥有不同的优势T细胞克隆,从而介导不同的免疫应答。因此,GD和TAO患者的特征性TCR可作为一种潜在的分子标志物。

Objective To establish the characteristic T cell receptor(TCR)repertoires which could distinguish the Graves′disease(GD)and thyroid associated ophthalmopathy(TAO)immune repertoire for precision diagnosis.Methods Fifteen Graves′disease patients(nine patients without Graves′ophthalmopathy and six with Graves′ophthalmopathy)were enrolled in this study,and they were diagnosed less than 2 months and were naive to treatment.Twenty healthy volunteers who were age and sex matched served as controls.The blood samples were collected at diagnosed.RNA was isolated for TCR repertoire sequencing.Results TCR diversity in GD and TAO patients was significantly lower than that of healthy controls.With TCR high-throughput sequencing data,characteristic TCR databases of GD and TAO,containing 157 and 116 VJ families,was constructed.In these VJ families,both common and unique families of the two diseases existed.Conclusion GD and TAO have common pathogenesis,but have different dominant T cell clones,which mediate different immune responses.Therefore,the characteristic TCR of GD and TAO patients may be used as a potential molecular marker.