Research on molecular mechanisms of break in immunological tolerance in disorders caused by single-gene defect

我们建立了多参数流式细胞术用于详细的免疫表型分析和KREC/TRECs分析用于评估B和T细胞新生，以深入研究原发性免疫缺陷（PID）中自身免疫的发病机制。 我们将PID患者分为几组，并建立了一个数据库，PID与自身免疫。我们开发了一种广泛的方法，使用高通量下一代测序（NGS）来分析IgH和TCR库，并开始测量10例患者的库。通过对40多例自身免疫性PID患者的全外显子组分析（WEA），我们在5例患者中发现了突变。 这些包括BTK，FANCA，LRBA，PIK 3CD和STAT 1。 通过对5名患者及其家人进行WEA，获得候选基因（范围为1至6个）。

We set up a multiparameter flow cytometry for detailed immunophenotyping and KRECs/TRECs analysis for assessment of B and T cell neogenesis, respectively in order to delve into pathogenesis of autoimmunity developed in primary immunodeficiency (PID). We categorized the PID patients into several groups and also established a database for PID with autoimmunity. We developed an extensive method to analyze IgH and TCR repertoires using high-throughput next generation sequencing (NGS), and started measuring the repertoire in 10 patients. Through whole exome analysis (WEA) for more than 40 PID patients with autoimmunity, we identified a mutation in 5 patients. These include BTK, FANCA, LRBA, PIK3CD, and STAT1. Candidate genes (ranging one to six) were obtained by carrying out WEA for a patient and his/her family members in 5 patients.