血栓性血小板减少性紫癜（TTP）是一种临床急重症，是由于人体内ADAMTS13酶基因缺陷（遗传性）或产生该酶抗体（获得性TTP）从而导致该酶活性丧失、无法水解底物VWF所致，临床以广泛微血管血栓形成和血小板减少为病理特征。血浆置换疗法的临床应用，对TTP急性发作期治疗效果虽有明显改观，但仍存在易反复发作等问题亟待解决。本课题拟对中国人群中获得性TTP中抑制ADAMTS13活性的自身抗体识别表位进行筛查，针对关键位点对ADAMTS13进行改造构建突变质粒，首次导入人外周血来源的过度生长内皮细胞（BOECs）,通过体外和体内实验观察ADAMTS13突变体的的表达和活性，同时监测导入NOD/SCID小鼠体内稳定转染的tBOECs在体内的分布和存活情况，为今后用于TTP的基因治疗提供理论和实验依据。

Thrombotic thrombocytopenic purpura (TTP) is an acute and severe disease, due to genetic deficiency of ADAMTS13 (genetic TTP) or production of the ADAMTS13 antibodies (acquired TTP), accompanied by loss of enzymatic activity to cleave VWF. The pathological characteristics usually exhibit extensive microvascular thrombus formation and platelet reduction. Clinical application of plasma exchange therapy on acute exacerbation of TTP is useful, but there are still many problems to be solved. This project aims to screen the recognition epitope of the autoantibody which inhibited the activity of ADAMTS13 from the Chinese population of acquired TTP. According to the key binding sites for ADAMTS13, modified mutant plasmid will be transfected into blood outgrowth endothelial cells (BOECs) for the first time. The activity of the ADAMTS13 mutant in vitro and in vivo experimental will be observed. And the distribution and survival of the stably transfected BOECs (tBOECs) in NOD/SCID mouse will also be investigated, which may provide theoretical and experimental evidence for gene therapy for TTP in the future.