Characterization of the lupus nephritis microRNAome

狼疮性肾炎 microRNAome 的表征

• 批准号: 10251046
• 负责人: Elizabeth E Brown
• 金额: $ 51.15万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-07 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10251046
• 关键词: Affect; African; African American; Age; American; Amerindian; Autoantibodies; Autoimmune Diseases; Bioinformatics; Biological; Biological Markers; Blood; Cell Communication; Cells; Clinical; Complement Activation; Complex; DNA Sequence; Data; Disease; Disease Surveillance; Early Diagnosis; Environmental Risk Factor; Epigenetic Process; Etiology; European; Female; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; Immune; Investigation; Kidney; Knowledge; Lupus; Lupus Nephritis; Malignant Neoplasms; Mediating; Membrane; MicroRNAs; Modeling; Monitor; Morbidity - disease rate; Nephritis; Organ; Participant; Pathogenesis; Pathogenicity; Patient risk; Patients; Peripheral Blood Lymphocyte; Persons; Phenotype; Play; Population; Property; Race; Renal Tissue; Resources; Risk; Role; Sampling; Serum; Severities; Specificity; Susceptibility Gene; Systemic Lupus Erythematosus; Testing; Time; Tissues; Translating; Untranslated RNA; Validation; Variant; Vesicle; Woman; case control; course development; diagnostic biomarker; ethnic minority population; exosome; functional genomics; improved; insight; miRNA expression profiling; mortality; new therapeutic target; next generation; novel marker; overexpression; preservation; prevent; specific biomarkers; targeted treatment; trait; transcriptome; transcriptome sequencing; trend

ABSTRACT The goal of this investigation is to identify and characterize the role of microRNAs (miRNA) in serum exosomes on the risk of Systemic Lupus Erythematosus (SLE), and among patients with SLE, the risk of, and rate of progression to, lupus nephritis (LN). SLE is a prototypic autoimmune disease that is characterized by the presence of antinuclear autoantibodies, complement activation and multisystem organ damage, including LN, which accounts for significant morbidity and mortality particularly among persons of African American and Amerindian ancestry. The basis for this disparity remains poorly understood. Although the etiology of SLE is unclear, combinations of genetic and environmental factors play a causal role. Despite the discovery of several SLE susceptibility loci, variation in DNA sequence alone accounts for only a small fraction of common complex disease and efforts to utilize these markers to classify or monitor SLE clinical course, and the development of LN, have not yet been successful. Recent advances in transcriptome sequencing offer new opportunities to characterize miRNAs as novel biomarkers, which could significantly change the paradigm of SLE clinical monitoring. We will test the overarching hypothesis that distinct serum exosome miRNAs will correlate with the presence of SLE and among patients with SLE, the presence of and time to, LN, and that miRNAs influence the severity and rate of progression of LN by altering target gene expression. We intend to capitalize on a unique opportunity to explore these relationships in a large, ancestry diverse, well-characterized population of established SLE while taking advantage of recent advances in bioinformatics and whole transcriptome sequencing. Our objective to characterize the influence of exosome miRNAs relative to the risk of SLE and among these patients, the risk and tempo of LN in paired blood and target tissue fills a critical gap in knowledge required to advance efforts to detect, prevent and manage LN among SLE patients, as well as to identify new therapeutic targets. Findings forthcoming from this investigation will fill a critical gap elated to the disparate trends of SLE etiology and progression, which differ by ancestry, and may translate to other kidney phenotypes including those observed in immune-mediated cancers.

抽象的 这项研究的目的是识别和表征microRNA（miRNA）在血清外泌体中的作用 全身性红斑狼疮（SLE）的风险，在有SLE的患者中，进展的风险和速率 狼疮肾炎（LN）。 SLE是一种原型自身免疫性疾病，其特征是存在抗核 自身抗体，补体激活和多系统器官损伤，包括LN，其中包括 尤其是在非裔美国人和美洲血统的人中的大量发病率和死亡率。这 这种差异的基础仍然很少理解。尽管SLE的病因尚不清楚，但遗传的组合 环境因素起因果作用。尽管发现了几个SLE敏感性基因座，但 仅DNA序列仅占常见复杂疾病的一小部分，并努力利用这些疾病 分类或监测SLE临床课程以及LN的发展的标记尚未成功。最近的 转录组测序的进步为将miRNA描述为新型生物标志物提供了新的机会， 可能会大大改变SLE临床监测的范例。我们将检验以下总体假设 独特的血清外泌体miRNA将与SLE的存在以及SLE患者的存在相关，存在 LN的时间和时间，以及miRNA通过改变靶基因而影响LN的严重程度和速率 表达。我们打算利用一个独特的机会来探索这些关系 多样化，良好的已建立SLE人群，同时利用最近的进步 生物信息学和整个转录组测序。我们表征外泌体影响的目标 相对于SLE风险和这些患者的miRNA，配对的血液和目标的LN风险和速度 组织填补了促进检测，预防和管理LN所需的知识的关键空白 患者以及确定新的治疗靶标。这项调查的发现将填补 关键的差距到SLE病因学和进展的不同趋势，这些趋势因祖先而有所不同，可能 转化为其他肾脏表型，包括在免疫介导的癌症中观察到的肾脏表型。