Small RNAs and risk of rheumatoid arthritis

小RNA与类风湿性关节炎的风险

• 批准号: 10368663
• 负责人: Michelle Jane Ormseth
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10368663
• 关键词: 2' -Deoxythymidine; Affect; Autoimmune Diseases; Autoimmunity; Bacteria; Basic Science; Bioinformatics; Biological Assay; Biological Markers; Chronic; Clinical; Clinical Data; Data; Department of Defense; Development; Diagnosis; Disease; Disease Marker; Disease remission; Early Intervention; Early treatment; Etiology; Feces; First Degree Relative; Goals; Hepatitis C Therapy; Human; Human Genome; In Vitro; Individual; Inflammatory; Interferons; Lead; Length; Link; Malignant Neoplasms; Maps; Measures; Mediator of activation protein; Membrane; Messenger RNA; MicroRNAs; Microbe; Nucleotides; Onset of illness; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Phase; Plasma; Play; RNA; Regulator Genes; Reporter Genes; Research; Rheumatoid Arthritis; Risk; Role; Sampling; Serology; Serum; Shotguns; Site; Small RNA; Specimen; Structure; Testing; Therapeutic; Time; Transfer RNA; Translating; Translations; Untranslated RNA; Validation; Vesicle; Veterans; Virulence Factors; accurate diagnosis; aggressive therapy; antagonist; cell type; clinical development; cohort; disability; drug response prediction; gene function; high risk; human disease; human microbiota; immune function; improved; innovation; insight; machine learning method; member; metagenomic sequencing; microbial; microbial genome; microbiome; microbiome alteration; microbiome components; mimetics; mortality; next generation sequence data; novel marker; novel therapeutics; outcome prediction; pre-clinical; predicting response; prevent; prospective; repository; response; screening; treatment response

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease affecting nearly 1% of Veterans. Early and aggressive treatment of RA improves likelihood of remission and reduces disability. Therefore, biomarkers identifying patients with high likelihood of developing disease could stratify individuals who would benefit from early interventions aimed at preventing disease and reducing disability. Such biomarkers may also provide insight into disease mechanisms. Our overarching goal is to determine the role of human and microbial sRNAs in the development of RA. The rationale for the proposed research is that sRNAs are powerful gene regulators and markers of disease. We have found that circulating human and microbial sRNAs are altered in established RA patients compared to control subjects, are associated with disease measures and can alter inflammatory cellular pathways. Building on preliminary data, we will define circulating human (Aim 1) and microbial (Aim 2) sRNAs that predict development of RA and change between preclinical and clinical RA in discovery and validation cohorts and identify the function of predictive sRNAs. Aim 3 will determine if microbiome alterations in new-onset untreated RA are reflected in alterations in plasma microbial sRNAs. The proposed research is significant because it will help us to identify patients with high likelihood of developing RA, enabling us to identify individuals who would benefit from early interventions aimed at preventing disease and reducing disability. The proposal is innovative because it has the potential to revolutionize our understanding of markers and mechanisms underlying development of RA and our understanding of how the human microbiota can influence immune function. The study is high impact because it could identify fundamental, targetable mechanisms underlying developing RA and could lead to targeted sRNA therapeutics.

类风湿关节炎（RA）是一种全身性炎症自身免疫性疾病，几乎影响 1％的退伍军人。 RA的早期和积极治疗可改善缓解的可能性和 减少残疾。因此，生物标志物鉴定出高可能发生的患者 疾病可以分层将从旨在防止的早期干预措施中受益的个人 疾病和减少残疾。这样的生物标志物也可能提供有关疾病的洞察力 机制。 我们的总体目标是确定人类和微生物SRNA在 RA的发展。拟议研究的理由是SRNA是强大的基因 疾病的监管因子和标记。我们发现循环人类和微生物SRNA 与对照组相比，已建立的RA患者的改变，与疾病有关 措施并可以改变炎症性细胞途径。 在初步数据的基础上，我们将定义循环人类（AIM 1）和微生物（AIM 2）SRNA预测RA的发展以及临床前和临床RA之间的变化 发现和验证队列并确定预测性SRNA的功能。目标3意志 确定未经处理的新型RA中的微生物组改变是否反映在变化中 血浆微生物SRNA。 拟议的研究很重要，因为它将帮助我们识别高的患者 开发RA的可能性，使我们能够确定可以从早期受益的个人 旨在预防疾病和减少残疾的干预措施。该提议是创新的 因为它有可能彻底改变我们对标记和机制的理解 RA的基本发展以及我们对人类微生物如何影响的理解 免疫功能。这项研究具有很高的影响，因为它可以识别基本的，可目标的 开发RA的基础机制，可能导致靶向SRNA疗法。