基于单细胞免疫组库测序技术的ITP患者免疫图谱构建及分型研究

原发免疫性血小板减少症（ITP）是一种自身免疫病，发病机制复杂，且具有个体异质性，进而造成临床疗效存在明显差异。细胞毒T细胞对血小板的裂解作用及抗血小板自身抗体的产生是血小板减少的两个主要途径。但目前临床上并未根据患病原因对患者进行免疫分型，大部分患者治疗依赖于医生经验性的选择治疗方案，导致患者疗程长、疗效差异大，甚至引发不良反应。因而，本研究拟以利妥昔单抗治疗反应差异为入口，收集利妥昔单抗治疗有效/无效患者治疗前后及正常对照外周血单个核细胞，进行10×Genomics单细胞免疫组库测序，并联合分析单细胞RNA-seq和免疫组库数据，构建ITP患者免疫图谱，从基因、细胞及生物学过程等层面上阐明ITP发病机制。另外，比较利妥昔单抗有效及无效患者的图谱，根据血小板破坏途径的不同尝试对ITP进行免疫分型，并通过动物实验筛选针对不同分型的最优治疗方案，最终推广至患者，初步实现个体化治疗。

Because of the complex pathogenesis and individual heterogeneity, the therapy response of primary immune thrombocytopenia (ITP) among patients is different. Cytotoxic T cells mediated lysis of platelets and the appearance of autoantibodies to platelets are main causes of thrombocytopenia. Currently, patients are not immunotyped according to the cause of the disease. Clinically, the treatment options of most patients depend on doctor’s experience, resulting in long treatment courses, great differences in efficacy, and even adverse reactions. Therefor, in this study, we intend to collect peripheral blood mononuclear cells of normal controls and ITP patients with effective/ineffective rituximab treatment, and perform 10 × Genomics single-cell immune repertoire sequencing; Following construct immune atlas of ITP patients by analyzing the single-cell RNA-seq and immune repertoire data, and finally elucidate the pathogenesis of ITP from the level of genes, cells and biological processes. In addition, through comparing the immune profiles of patients with effective/ ineffective rituximab treatment, we will try to immunotype the ITP patients according to different platelet destruction pathways, and select the best treatment plan for different types by animal models, eventually extend to patients, and initially achieve individualized treatment.