Graves 病是一种多基因遗传性自身免疫性甲状腺疾病，B细胞分泌致病性TSAb是发病机制中关键的一环。申请人在前期通过circRNAs芯片筛选发现Graves病患者外周血外泌体中circRNA 1421表达特异性降低。同时通过生物信息学分析，预测circRNA 1421可能作为竞争性内源RNA(ceRNA)靶向miR-22/miR-16调节PETN蛋白表达。PTEN作为B细胞的负调控信号蛋白，下调导致B细胞活化分泌TSAb致Graves病。本项目拟在此基础上，采用基因过表达、沉默、FISH、RIP、双荧光素酶报告基因等技术，在临床和离体细胞水平展开系列深入研究。以期阐明外泌体circRNA 1421调控PTEN表达活化B细胞生成TSAb在Graves病发病中的作用分子机制。解析Graves病B细胞产生TSAb的细胞间通讯表观遗传学机制，为Graves病治疗的新靶点提供科学依据。

B cells secreting pathognomonic thyroid-stimulating autoantibodies（TSAb） plays an important role in Graves disease, a polygenetic hereditary autoimmune thyroid disease. Our previous study revealed the expression of circRNA 1421 is decreasing in the B cells of Graves disease by circRNAs Microarray. At the same time through bioinformatics analysis, we speculated circRNA 1421 may control PETN expression as ceRNA targeted miR-22/miR-16.Decreased PTEN, a negative regulatory protein in B cells，induces activating B cells producing pathogenic antibody TSAb. Based on the documents and our previous studies, we aim to discuss molecular mechanism in Graves disease-exosomal circRNA1421 activate B cells producing TSAb via controlling PTEN expression using gene overexpression, gene silencing, FISH, RIP, dual luciferase report gene in clinical and in vitro. Research of epigenetic regulating mechanisms in TSAb production provides a scientific basis for novel targets for Graves disease therapy.