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Inflammatory dysregulation of vaccine responses in sickle cell disease

镰状细胞病疫苗反应的炎症失调

基本信息

批准号：
10617772
负责人：
RUTH R MONTGOMERY
金额：
$ 47.86万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-12 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10617772
关键词：
Acute Adjuvant Affect African American population Age Aging Amino Acid Substitution Antibodies Appearance B-Lymphocytes Biological Assay Blood Platelets Blood specimen Bone necrosis Cell Lineage Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Chronic Clinical Data Data Analyses Data Set Development Enzyme-Linked Immunosorbent Assay Erythrocyte Membrane Frequencies Functional disorder Gene Expression Genetic Genetic Transcription Hematological Disease Heme Hemolysis Hydrophobicity Immune Immune response Immunity Immunoglobulin A Immunoglobulin M Immunologic Markers Immunologic Stimulation Immunologics Impairment In Situ Income Infection Inflammasome Inflammatory Investigation Iron Ischemia Life Expectancy Ligands MF59 Mass Spectrum Analysis Memory B-Lymphocyte Microcirculation Modality Modeling Molecular Profiling Natural Immunity Organ Pain Pathway interactions Patients Pattern recognition receptor Peripheral Blood Mononuclear Cell Phenotype Point Mutation Polyvalent pneumococcal vaccine Predisposition Production Proteomics Pulmonary Hypertension Recurrence Retinal Diseases Serotyping Serum Proteins Severity of illness Shapes Sickle Cell Sickle Cell Anemia Skin Streptococcus pneumoniae Stroke System T cell response T-Lymphocyte Subsets TLR4 gene Therapeutic Transfusion United States Vaccination Vaccines Vulnerable Populations Whole Blood adaptive immunity beta Globin cytokine data management flu global health hemoglobin polymer hydroxyurea immunological status improved inflammatory milieu influenza virus vaccine lymph node biopsy neutrophil patient population protein biomarkers responders and non-responders response seroconversion sickling single cell technology transcriptomics vaccination strategy vaccine efficacy vaccine response vascular abnormality

项目摘要

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.

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。