MicroRNA Profiling of Pediatric Immunodeficiency Patients

儿童免疫缺陷患者的 MicroRNA 分析

• 批准号: 7934643
• 负责人: NICOLAI Stanislas Cyrille VAN OERS
• 金额: $ 19.43万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-21 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934643
• 关键词: Autoimmunity; Biological Assay; Biological Process; Blood specimen; Cells; Child; Childhood; Development; Diagnosis; Diagnostic; Disease Outcome; Foundations; Genes; Goals; Health; Human; Immune; Immune response; Immune system; Immunoglobulin M; Immunologic Deficiency Syndromes; Infection; Intervention; Life; Link; Malignant Neoplasms; Measures; Medical; MicroRNAs; Molecular; Molecular Profiling; Mutation; NIH Program Announcements; Parasitic infection; Patients; Pattern; Population; Process; Recurrence; Screening procedure; Small RNA; Source; Syndrome; Therapeutic; Tissues; Viral; Virus Diseases; base; improved; innovation; novel diagnostics; peripheral blood; prognostic; prognostic indicator; prophylactic; public health relevance; tumorigenesis

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.

描述（由申请人提供）：儿科免疫缺陷（PID）通常导致儿童危及生命的感染。超过150个基因的突变与这些免疫缺陷有关。然而，鉴定导致PID的突变的过程是极其劳动密集型的，并且通常不成功。我们建议为患有PID的儿童开发microRNA谱。MicroRNA是最近发现的一类小RNA，可调节多种生物过程，包括免疫细胞发育和癌症。重要的是，microRNA谱正在成为肿瘤发生和自身免疫的关键诊断和预后指标。我们假设患有PID的儿童将表达与正常对照不同的microRNA特征谱。将为不同的DiGeorge和高IgM患者开发MicroRNA阵列签名谱。在不同PID中检测到的特定类型的microRNA也将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引入预防性治疗，并在不同的PID中识别癌症潜力。公共卫生相关性：先天免疫系统和适应性免疫系统的细胞协调发挥作用，以消除细菌和病毒感染。一旦它们对感染做出反应，免疫细胞就会经历许多发育变化，其中一些由称为microRNA的小RNA分子控制。我们建议开发儿童免疫缺陷患者的microRNA阵列谱。来自这种分析的信息将为患有各种免疫缺陷的患者提供大大改进的诊断和预后措施。

项目成果

Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome.

• DOI: 10.1016/j.clim.2013.01.011
• 发表时间: 2013-04
• 期刊: Clinical immunology (Orlando, Fla.)
• 作者: de la Morena MT;Eitson JL;Dozmorov IM;Belkaya S;Hoover AR;Anguiano E;Pascual MV;van Oers NSC
• 通讯作者: van Oers NSC

Transgenic expression of microRNA-181d augments the stress-sensitivity of CD4(+)CD8(+) thymocytes.

• DOI: 10.1371/journal.pone.0085274
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Belkaya S;van Oers NS
• 通讯作者: van Oers NS