MicroRNA Profiling of Pediatric Immunodeficiency Patients

描述(由申请人提供)：儿童免疫缺陷(PID)通常会导致儿童受到危及生命的感染。超过150个基因的突变与这些免疫缺陷有关。然而，识别导致ID的突变的过程是极其劳动密集型的，而且往往不成功。我们建议为患有PID的儿童开发一种microRNA简档。MicroRNAs是最近发现的一类小RNA，它调节包括免疫细胞发育和癌症在内的各种生物学过程。重要的是，microRNA图谱正在成为肿瘤发生和自身免疫的关键诊断和预后指标。我们假设，使用PID的儿童将表现出与正常对照组不同的microRNA签名特征。将为不同的DiGeorge和高IgM患者开发microRNA阵列签名配置文件。在不同的PID中检测到的特定类型的microRNAs也将被用作癌症或感染等并发症的预后指标。这将使临床医生能够介绍预防性治疗，并在不同的ID中识别癌症潜力。公共卫生相关性：先天免疫系统和获得性免疫系统的细胞协调起作用，以消除细菌和病毒感染。一旦免疫细胞对感染做出反应，它们就会经历一系列发育变化，其中一些变化由称为microRNAs的小RNA分子控制。我们建议开发表现为儿科免疫缺陷患者的microRNA阵列。这种分析的信息将为各种免疫缺陷患者提供极大改善的诊断和预后措施。

DESCRIPTION (provided by applicant): Pediatric immunodeficiencies (PIDs) often result in life-threatening infections in children. Mutations in over 150 genes have been linked to these immunodeficiencies. However, the process of identifying mutations that result in PIDs is extremely labor intensive, and often not successful. We propose to develop a microRNA profile for children presenting with PIDs. MicroRNAs are a recently discovered class of small RNAs that regulate diverse biological processes including immune cell development and cancers. Importantly, microRNA profiling is emerging as a key diagnostic and prognostic indicator of tumorigenesis and autoimmunity. We hypothesize that children presenting with PIDs will express microRNA signature profiles distinct from normal controls. MicroRNA array signature profiles will be developed for diverse DiGeorge and hyper-IgM patients. The particular types of microRNAs detected in different PIDs will also be used as a prognostic indicator for complications such as cancers or infections. This will enable clinicians to introduce prophylactic therapies and recognize cancer potentials among diverse PIDs. PUBLIC HEALTH RELEVANCE: The cells of the innate and adaptive immune system coordinately function to eliminate bacterial and viral infections. Once they respond to an infection, the immune cells undergo a number of developmental changes, some of which are controlled by small RNA molecules called microRNAs. We propose to develop microRNA array profiles of patients presenting with pediatric immunodeficiencies. The information from such profiling will provide vastly improved diagnostic and prognostic measures for patients with various immunodeficiencies.