Identification of Plasma microRNA Expression Profile in Ankylosing Spondylitis.

强直性脊柱炎血浆 microRNA 表达谱的鉴定。

基本信息

批准号：
8907904
负责人：
Tariq M Haqqi
金额：
$ 15.89万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-07 至 2018-01-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Our understanding of the cellular and molecular pathways driving the pathogenesis in ankylosing spondylitis (AS) is still very incomplete. One of the key challenges in management of AS is lack of specific markers of disease activity. Aberrant expression of microRNAs (miRNAs) has been identified in various diseases. Recent studies demonstrated that miRNAs can be detected in the circulation and serve as potential biomarkers of various diseases. Moreover, the detection of circulating miRNAs can provide important novel information concerning diseases. At present there are no studies that have established a miRNA based signature profile in patients with AS. Given these findings, we hypothesize that patients with AS have aberrantly expressed circulating miRNAs reflective of underlying disease and inflammation and these dysregulated miRNAs can be detected through miRNA expression profiling. We further hypothesize that certain specific dysregulated candidate miRNAs in plasma of patients with AS will correlate with disease activity measures like Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). These hypotheses will be addressed in the experiments of the following specific Aims: (1) to determine the expression profile of miRNAs in plasma of patients with AS and compare it with healthy, age and sex-matched controls. (2) To test whether the expression of the specific miRNAs identified in aim-1 correlates with disease activity in AS as measured by BASDAI and ASDAS. Should the exploratory study reveal a correlation between specific miRNAs in the plasma of patients with AS and disease activity measures, they may represent potential biomarkers of disease activity in AS. These potential biomarkers of disease activity in AS can be validated in future large clinical studies and may have significant impact on management of AS.

描述（由申请人提供）：我们对驱动强直性脊柱炎（AS）发病机制的细胞和分子途径的理解仍然非常不完整。 AS 管理的主要挑战之一是缺乏疾病活动的特异性标志物。已在多种疾病中发现 microRNA (miRNA) 的异常表达。最近的研究表明，miRNA 可以在循环中检测到，并可作为各种疾病的潜在生物标志物。此外，循环 miRNA 的检测可以提供有关疾病的重要新信息。目前还没有研究在 AS 患者中建立基于 miRNA 的特征谱。鉴于这些发现，我们假设 AS 患者异常表达循环 miRNA，反映了潜在的疾病和炎症，并且可以通过 miRNA 表达谱检测这些失调的 miRNA。我们进一步假设 AS 患者血浆中某些特定的失调候选 miRNA 将与巴斯强直性脊柱炎疾病活动指数 (BASDAI) 和强直性脊柱炎疾病活动评分 (ASDAS) 等疾病活动指标相关。这些假设将在以下具体目标的实验中得到解决：（1）确定AS患者血浆中miRNA的表达谱，并将其与健康、年龄和性别匹配的对照进行比较。 (2)测试aim-1中鉴定的特定miRNA的表达是否与通过BASDAI和ASDAS测量的AS疾病活动性相关。如果探索性研究揭示 AS 患者血浆中的特定 miRNA 与疾病活动性指标之间的相关性，它们可能代表 AS 疾病活动性的潜在生物标志物。这些潜在的 AS 疾病活动生物标志物可以在未来的大型临床研究中得到验证，并可能对 AS 的管理产生重大影响。