Identification of Plasma microRNA Expression Profile in Ankylosing Spondylitis.

描述(由申请人提供)：我们对强直性脊柱炎(AS)发病机制的细胞和分子途径的了解仍然很不完整。管理AS的关键挑战之一是缺乏疾病活动的特定标记物。MicroRNAs(MiRNAs)的异常表达在多种疾病中被发现。最近的研究表明，miRNAs可以在血液循环中检测到，并作为各种疾病的潜在生物标志物。此外，检测循环中的miRNAs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的特征图谱。鉴于这些发现，我们假设AS患者异常表达了反映潜在疾病和炎症的循环miRNAs，这些失调的miRNAs可以通过miRNA表达谱检测到。我们进一步假设AS患者血浆中某些特定的异常候选miRNAs将与Bath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。这些假设将在以下特定目的的实验中得到解决：(1)测定AS患者血浆中miRNAs的表达谱，并将其与健康、年龄和性别匹配的对照组进行比较。(2)检测AIM-1中鉴定的特定miRNAs的表达是否与BASDAI和ASDAS测定的AS疾病活动性相关。如果探索性研究揭示了AS患者血浆中特定的miRNAs与疾病活动指标之间的相关性，它们可能是AS疾病活动的潜在生物标志物。这些潜在的AS疾病活动性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。

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.