Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis

慢性过敏性肺炎预后转录组特征的开发和验证

基本信息

  • 批准号:
    10454852
  • 负责人:
  • 金额:
    $ 34.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT: Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease, resulting from inhalational exposure to a large variety of antigens. For unknown reasons, a subgroup of patients with HP without a known inciting antigen exposure develops chronic disease with progressive pulmonary fibrosis (the leading cause of death). Accurately identifying patients at risk of disease progression is necessary for prognosis and therapy. The objective of this proposal is to refine our current clinical risk stratification by identifying and validating a transcriptomic signature from peripheral blood mononuclear cells in patients with chronic HP that is predictive of disease progression. We hypothesize that the clinical course of chronic HP is associated with a peripheral blood gene expression signature of risk that can be used to refine the prognosis and predict the clinical outcome. Guided by strong preliminary data, this hypothesis will be tested by two specific aims: i) Establish transcriptomic signatures at time of initial presentation in peripheral blood mononuclear cells from patients with chronic HP in a Discovery cohort and then validate the signature in an independent chronic HP replication cohort; and ii) Establish a time-course transcriptomic profile predictive of disease progression in the Discovery cohort and validate the signature profile in the independent chronic HP replication cohort. pursuing The proposed research is significant because it will provide the knowledge that will enhance our ability to predict disease progression, a level of prognostication which is not possible with current clinical measures alone. Relevance to Public Health: This is an important and under-investigated area that has the potential to fundamentally advance our understanding of the pathobiology of disease progression and provide the groundwork to define molecular targets relevant to chronic HP disease progression.
项目总结/摘要:过敏性肺炎(HP)是一种免疫介导的 肺部疾病,由于吸入暴露于各种抗原。由于未知的原因,A 没有已知的激发抗原暴露的HP患者亚组发展为慢性疾病, 进行性肺纤维化(死亡的主要原因)。准确识别存在疾病风险的患者 进展对于预后和治疗是必要的。该提案的目的是完善我们目前的临床 通过识别和验证来自外周血单核细胞的转录组标签进行风险分层 在慢性HP患者中,可预测疾病进展。我们假设, 慢性HP与外周血风险基因表达特征相关,该特征可用于细化 预后和预测临床结果。在强有力的初步数据的指导下,这一假设将得到检验, 两个具体目标:i)在外周血中初始呈现时建立转录组学签名 来自Discovery队列中慢性HP患者的单核细胞,然后在 独立的慢性HP复制组群;和ii)建立预测HP复制的时程转录组学谱, 在Discovery队列中评估疾病进展,并验证独立慢性HP 重复队列 追求 拟议的研究是重要的,因为它将提供的知识,将提高 我们预测疾病进展的能力,这是目前临床上不可能达到的一种精确水平。 措施单独。与公共卫生的相关性:这是一个重要但调查不足的领域, 有可能从根本上推进我们对疾病进展的病理生物学的理解, 确定与慢性HP疾病进展相关的分子靶点的基础。

项目成果

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Evans Fernandez其他文献

Evans Fernandez的其他文献

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{{ truncateString('Evans Fernandez', 18)}}的其他基金

Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis
慢性过敏性肺炎预后转录组特征的开发和验证
  • 批准号:
    10688186
  • 财政年份:
    2020
  • 资助金额:
    $ 34.29万
  • 项目类别:
Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis
慢性过敏性肺炎预后转录组特征的开发和验证
  • 批准号:
    10224321
  • 财政年份:
    2020
  • 资助金额:
    $ 34.29万
  • 项目类别:
Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis
慢性过敏性肺炎预后转录组特征的开发和验证
  • 批准号:
    9973969
  • 财政年份:
    2020
  • 资助金额:
    $ 34.29万
  • 项目类别:

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