Inflammatory dysregulation of vaccine responses in sickle cell disease

摘要 镰状细胞病（镰状细胞）是美国最常见的遗传性血液病， 日益严重的全球健康问题。镰状细胞病患者具有一系列急性和慢性多系统临床 并发症和预期寿命大大缩短。奇怪的是，尽管他们处于高度炎症状态， 镰状细胞患者对疫苗接种的反应降低，表明免疫调节失调或受损， 这让人想起我们对衰老过程中慢性炎症环境的研究。一个广泛的调查 镰状细胞病患者的全身免疫应答对于了解是否 慢性炎症性免疫状态可能导致对感染的易感性增加， 疫苗接种在这个脆弱的群体。我们将利用单细胞技术的最新进展 量化和分析镰状细胞病患者的免疫状态和对疫苗接种的反应。我们的研究将 提供深入的多参数免疫概况和分析，以确定定义免疫缺陷的分子特征。 在镰状细胞病患者群体中的高炎症状态和降低的疫苗效力。

Abstract Sickle cell disease (sickle cell) is the most common genetic hematologic disorder in the United States and an increasing global health problem. Sickle cell patients have a range of acute and chronic multisystem clinical complications and considerably shortened life expectancy. Paradoxically, despite their hyperinflammatory state, sickle cell patients have reduced responses to vaccination, suggesting dysregulation or impairments in immune pathways reminiscent of our studies of the chronic inflammatory milieu in aging. A broad investigation of the systemic immune response in patients with sickle cell disease is necessary for the understanding of whether chronic hyperinflammatory immune status may contribute to increased susceptibility to infections and reduced responses to vaccines in this vulnerable population. We will employ recent advances in single-cell technologies to quantify and analyze sickle cell disease patient immune status and responses to vaccinations. Our study will provide in-depth multiparameter immune profiles and analysis to identify molecular signatures defining the hyperinflammatory state and reduced vaccine efficacy in sickle cell disease patient populations.