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实质性疾病，具有不同的 炎症和纤维化程度。在最常见的纤维化性ILDS中，有前驱炎症 慢性过敏性肺炎(CHP)和结缔组织病相关性ILD(CTD-ILD)。 相当大比例的慢性幽门螺杆菌和CTD-ILD患者发展为进行性表型，该表型为阴性 影响生存和生活质量。这两种情况通常都用免疫抑制疗法治疗， 现在也可能受益于抗纤维化治疗。因为一些患者在没有治疗的情况下会保持稳定， 迫切需要更可靠地识别CHP和CTD-ILD患者，这些患者将发展为进展性 ILD，并为这类患者确定最佳治疗策略。这项提案旨在解决这一差距， 应用蛋白质组学方法识别预测进行性ILD的炎性蛋白的知识 CHP和CTD-ILD患者的免疫抑制反应不同。这项建议将为 为后续的有针对性的蛋白质研究奠定基础，这将促进生物标记物的开发 指导这类患者的临床决策。

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.