Interrogation of the inflammasome to identify biomarkers of progressive interstitial lung disease

项目摘要 间质性肺疾病（ILD）包括一组不同的弥漫性肺实质疾病， 炎症和纤维化的程度。最常见的伴有炎症的纤维化ILD包括 慢性过敏性肺炎（CHP）和结缔组织病相关ILD（CTD-ILD）。 相当比例的CHP和CTD-ILD患者发展为进行性表型， 影响生存和生活质量。这两种情况通常用免疫抑制疗法治疗， 现在也可以从抗纤维化治疗中获益。因为有些病人在没有治疗的情况下会保持稳定， 迫切需要更可靠地识别将发展为进行性的CHP和CTD-ILD患者， ILD并为此类患者确定最佳治疗策略。该提案旨在解决这一差距， 通过采用蛋白质组学方法鉴定可预测进行性ILD的炎症蛋白 CHP和CTD-ILD患者的免疫抑制剂应答存在差异。这项提案将奠定 为随后的靶向蛋白质研究奠定基础，这将促进生物标志物的开发， 指导该患者人群的临床决策。

Project Summary Interstitial lung disease (ILD) comprises a diverse group of diffuse parenchymal disorders with variable degrees of inflammation and fibrosis. Among the most common fibrosing ILDs with preceding inflammation are chronic hypersensitivity pneumonitis (CHP) and connective tissue disease-associated ILD (CTD-ILD). Substantial proportions of patients with CHP and CTD-ILD develop a progressive phenotype, which negative impacts survival and quality of life. Both conditions are generally treated with immunosuppressive therapy and may now also benefit from anti-fibrotic therapy. Because some patients will remain stable without therapy, there exists a critical need to more reliably identify CHP and CTD-ILD patients that will develop progressive ILD and define an optimal treatment strategy for such patients. This proposal seeks to address this gap in knowledge by employing a proteomic approach to identify inflammatory proteins predictive of progressive ILD and differential immunosuppressant response in patients with CHP and CTD-ILD. This proposal will lay the foundation for subsequent targeted protein investigation that will facilitate the development of biomarkers to guide clinical decision making in this patient population.