Systems Immunology profiling of respiratory viral infections in vulnerable populations

易感人群呼吸道病毒感染的系统免疫学分析

• 批准号: 10598132
• 负责人: Carmen R Mikacenic
• 金额: $ 31.6万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-29 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598132
• 关键词: Acute; Address; Adult; Affect; Anti-citrullinated peptide antibody; Antibodies; Antibody Formation; Antigens; Autoantibodies; Autoantigens; Autoimmune; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; B-cell receptor repertoire sequencing; Blood specimen; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Chronic; Clinical; Cytometry; Data; Data Analyses; Detection; Development; Disease; Disease Progression; Enrollment; Epithelium; Extracellular Matrix; Frequencies; General Population; Generations; Genetic; Genomics; Goals; Health Expenditures; Immune; Immune response; Immunoglobulin A; Immunologic Factors; Immunology; Immunophenotyping; Immunosuppression; Individual; Infection; Inflammation; Investigation; Kinetics; Lung; Measures; Membrane Proteins; Methods; Methylation; Molecular; Morbidity - disease rate; Mucosal Immune Responses; Mucositis; Mucous Membrane; Multiomic Data; Nose; Outcome; Parainfluenza; Pathogenesis; Pathway interactions; Patients; Peptides; Phenotype; Population; Proteome; Research Project Grants; Resolution; Respiratory Disease; Respiratory Mucosa; Respiratory Tract Infections; Rheumatoid Arthritis; Rhinovirus; Risk; Sampling; Seasons; Severities; Severity of illness; Specificity; Sputum; Standardization; System; Systemic disease; T-Lymphocyte; Tenascin; Testing; Time; Tissues; Vimentin; Viral; Viral Respiratory Tract Infection; Virus; Vulnerable Populations; acute infection; adaptive immune response; autoimmune pathogenesis; autoreactivity; extracellular; high dimensionality; infection risk; insight; methylome; mortality; multiple omics; nasal swab; neutrophil; novel; peripheral blood; programs; proteogenomics; pulmonary function; respiratory; respiratory virus; response; sample collection; single-cell RNA sequencing; spatiotemporal; systemic autoimmune disease; systemic autoimmunity; systemic inflammatory response; transcriptome

PROJECT SUMMARY/ABSTRACT – PROJECT 2 Acute respiratory viral infections (ARVI) are the most frequently occurring global illness producing significant morbidity and mortality, particularly in vulnerable populations. Adults with rheumatoid arthritis (RA) have an increased risk for infection and respiratory mucosal inflammation may contribute to autoimmune disease severity. The goal of this research project is to understand the molecular and cellular immune signatures of the RA response to ARVI to determine how this affects infection severity and autoimmune disease progression. The project includes a detailed systems immunology assessment of acute and long-term airway and adaptive systemic immune responses to naturally occurring ARVI. Project 2 will examine these responses in patients with early RA and established RA on immunosuppression and compare these responses to matched healthy controls. This project is synergistic with the overall program by utilizing similar sample types, timing of sample collection, and common clinical endpoints but differs by studying a distinct host. The individual projects benefit from the overall program's shared multi-omics approaches through a Genomics Core for the samples processing and generation of airway host transcriptome, proteome, epithelial methylation, and viral quantity and expression data, along with host genetics. There is also a shared Adaptive Phenotyping Core for the generation of high dimensional cytometry data to broadly characterize immune cell phenotypes and for detailed identification of antigen-specific cells. The first aim is to determine differences in respiratory innate immune profiles in pre/early RA, established RA, and healthy controls in response to ARVI using a multi-omics approach. The second aim will determine if there are differences in adaptive cellular responses including a detailed characterization of viral-specific and autoantigen specific populations. The third aim will utilize TotalSeq (scRNA-seq, TCR/BCR sequencing and surface protein quantification), to determine the relationship between mucosal and systemic responses. This study will determine both how mucosal inflammation contributes to autoimmune pathogenesis and the host response to ARVI. It will produce novel mechanistic insights into the diversity and commonality of adult and RA immune response to acute respiratory viruses and use cutting-edge methods to provide mechanistic insights.

项目摘要/摘要 - 项目2 急性呼吸道病毒感染（ARVI）是最常见的全球疾病，产生明显的明显 发病率和死亡率，尤其是在弱势群体中。类风湿关节炎（RA）的成年人有 感染和呼吸道粘膜感染的风险增加可能导致自身免疫性疾病 严重程度。该研究项目的目的是了解分子和细胞免疫特征 RA对ARVI的反应确定这如何影响感染严重程度和自身免疫性疾病进展。 该项目包括急性和长期气道和适应性的详细系统免疫学评估 系统性免疫反应对天然发生的ARVI。项目2将检查患者的这些反应 随着RA的早期和RA，对免疫抑制进行了RA，并将这些反应与匹配的健康进行比较 控件。该项目通过使用类似的样本类型，样本的时间来协同与整个程序协同作用 收集和常见的临床终点，但通过研究独特的宿主而有所不同。各个项目受益 从总体程序的共享多摩斯方法通过样本的基因组核心 气道宿主转录组，蛋白质组，上皮甲基化和病毒量的处理和生成 和表达数据，以及宿主遗传学。还有一个共同的自适应表型核心 高维细胞术数据的产生，以广泛表征免疫球表型和详细的表征 鉴定抗原特异性细胞。第一个目的是确定呼吸有先天免疫的差异 使用多摩尼斯 方法。第二个目标将确定自适应细胞反应是否存在差异 病毒特异性和自身抗原特定种群的详细表征。第三个目标将利用 TotalSeq（SCRNA-SEQ，TCR/BCR测序和表面蛋白质定量），以确定关系 在粘膜和全身反应之间。这项研究将决定粘膜炎症 有助于自身免疫发病机理和对ARVI的宿主反应。它将产生新颖的机械 对成人对急性呼吸道病毒的多样性和RA免疫反应的见解以及 使用尖端方法提供机械见解。