Small RNAs and risk of rheumatoid arthritis

类风湿关节炎(RA)是一种全身性炎症性自身免疫性疾病， 1%的退伍军人。早期积极治疗类风湿关节炎可提高缓解和缓解的可能性 减少残疾。因此，识别高发疾病患者的生物标志物 疾病可能使个人分层，这些人将从旨在预防的早期干预中受益 疾病和减少残疾。这样的生物标记物也可能提供对疾病的洞察 机械装置。 我们的首要目标是确定人类和微生物sRNA在 类风湿关节炎的发展。提出这项研究的理由是，sRNA是强大的基因。 疾病的监管者和标志物。我们已经发现，循环中的人类和微生物sRNA 在已确诊的类风湿关节炎患者中与对照组相比发生改变，与疾病有关 测量并可以改变炎症细胞途径。 根据初步数据，我们将定义循环人(AIM 1)和微生物(AIM 2)预测类风湿关节炎发生发展及临床前期和临床类风湿性关节炎变化的sRNA 发现和验证队列，并确定预测性sRNA的功能。目标3将 确定新发病的未经治疗的类风湿性关节炎患者的微生物组改变是否反映在 血浆微生物sRNA。 这项拟议的研究具有重要意义，因为它将帮助我们识别患有高血压病的患者。 发展类风湿性关节炎的可能性，使我们能够识别将从早期受益的个人 旨在预防疾病和减少残疾的干预措施。这项提议是创新的。 因为它有可能彻底改变我们对标志物和机制的理解 类风湿性关节炎的潜在发展和我们对人类微生物区系如何影响的理解 免疫功能。这项研究的影响很大，因为它可以确定基本的、有针对性的 发生类风湿性关节炎的潜在机制，并可能导致靶向sRNA疗法。

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.