Inflammatory dysregulation of vaccine responses in sickle cell disease

摘要 镰状细胞病是美国最常见的遗传性血液病 日益严重的全球健康问题。镰状细胞患者有一系列急性和慢性多系统临床 并发症和预期寿命显著缩短。矛盾的是，尽管他们处于高度炎症状态， 镰状细胞患者对接种疫苗的反应降低，表明免疫调节失调或受损。 这些途径让人想起我们对衰老中慢性炎症环境的研究。对这一事件的广泛调查 镰状细胞病患者的系统免疫反应对于了解 慢性高炎性免疫状态可能导致感染易感性增加和减少 这一脆弱人群对疫苗的反应。我们将采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简档和分析，以识别定义 镰状细胞病患者群体的高炎症状态和疫苗效力降低。

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.