Defining New Human Immunodeficiency and Immunodysregulation Disorders

除了缺乏已知诊断的独特免疫缺陷和免疫失调患者外，我们接受的治疗还包括联合免疫缺陷、常见变量免疫缺陷(CVID)、变异型高IgE综合征或自身免疫淋巴增殖性综合征(ALPS)、Evans综合征、caspase-8缺陷状态(CEDS)、B细胞增殖伴核因子-kB和T细胞无能(Benta)病、X连锁镁缺陷合并EBV感染和肿瘤(XMEN)、Pasli(p110 Delta激活突变导致T细胞衰老、淋巴病变和免疫缺陷)疾病，以及Chai(CTLA4单倍体功能不全伴自身免疫渗透)疾病。对EBV、鼻病毒、流感病毒和呼吸道合胞病毒易感性的患者也进行了调查。我们的评估包括功能筛选和基因测序，还使用生化分析、基因表达微阵列、流式细胞仪分析、体外功能测试和其他技术对部分患者进行了深入研究。这些实验为以前与疾病无关的新候选基因的测序提供了线索。此外，我们正在使用比较基因组杂交(CGH)阵列、全外显子组测序、全基因组测序和其他技术，以公正的方式确定新的免疫性疾病的遗传原因。 在2016财年，我们还与NIH临床中心和NHGRI启动了一项合作研究，旨在识别新的免疫疾病的潜在单基因原因，而且旨在将整个外显子测序中发现的偶然遗传发现整合到临床实践中。其他正在进行的合作研究包括调查帕斯利和柴氏病的自然病史和最佳治疗方法。

Besides unique patients with immunodeficiency and immunodysregulation disorders lacking known diagnoses, our intake includes patients with combined immunodeficiency, common variable immunodeficiency (CVID), variants of hyper-IgE syndrome or autoimmune lymphoproliferative syndrome (ALPS), Evans syndrome, caspase-8-deficiency state (CEDS), B cell expansion with NF-kB and T cell anergy (BENTA) disease, X-linked Magnesium defect with EBV infection and Neoplasia (XMEN), PASLI (p110 delta activation mutation causing senescent T cells, lymphadenopathy, and immunodeficiency) disease, and CHAI (CTLA4 haploinsufficiency with autoimmune infiltration) disease. Patients with EBV, rhinovirus, influenza virus, and respiratory syncytial virus susceptibility have also been investigated. Our evaluation includes functional screening and gene sequencing, and a subset of patients is also being intensively studied using biochemical analyses, gene expression microarrays, flow cytometric analyses, in vitro functional tests, and other technologies. These experiments have provided leads for sequencing of new candidate genes not previously associated with disease. Additionally, we are using comparative genomic hybridization (CGH) arrays, whole exome sequencing, whole genome sequencing, and other technologies to determine genetic causes of new immunological diseases in an unbiased manner. In FY2016, we also initiated a collaborative study with the NIH Clinical Center and NHGRI that is aimed not only at identifying underlying monogenetic causes of novel immune disorders, but also is aimed at integrating into clinical practice incidental genetic findings found on whole exome sequencing. Other ongoing collaborative studies involve investigating the natural history and optimal treatment for PASLI and CHAI diseases.