Systems Biology Approach to Study Influenza Vaccine in Children with Autoimmunity

研究自身免疫儿童流感疫苗的系统生物学方法

• 批准号: 8307075
• 负责人: Maria Virginia Pascual
• 金额: $ 30.86万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-05 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307075
• 关键词: Address; Adolescent; Adult; Adverse event; Antibody Formation; Antinuclear Antibodies; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Award; B cell differentiation; B-Lymphocytes; Biological Markers; Blood; CD4 Positive T Lymphocytes; Cells; Child; Childhood; Clinical; Data; Dendritic Cells; Disease; Disease Marker; Dose; Enrollment; Epidemiology; Event; Flare; General Population; Generations; Genes; Genomics; Glucocorticoids; Helper-Inducer T-Lymphocyte; Human; Hydroxychloroquine; Immune; Immune response; Immune system; Immunization; Individual; Infection; Influenza; Influenza vaccination; Instruction; Interferon-alpha; Interferons; Light; Lupus; Measures; Methotrexate; Nuclear Antigens; Oral; Pathway interactions; Patients; Plasma Cells; Play; Reporting; Role; Specificity; Staging; Symptoms; Systemic Lupus Erythematosus; Systems Analysis; Systems Biology; Testing; Tissues; Vaccinated; Vaccination; Vaccines; Validation; cohort; influenza virus vaccine; macrophage; monocyte; novel; response

Current influenza vaccines are considered safe and effective for the general population, but post-vaccination adverse events, including autoimmune manifestiations, have been described in previously healthy individuals. Although infections, including influenza, can trigger flares in patients with autoimmune diseases, whether or not to vaccinate these patients remains a subject of discussion. In adult patients with systemic lupus erythematosus (SLE), influenza vaccine has been reported to be safe for those with quiescent disease but is not recommended for patients with active disease. Vaccination is not considered to be a causal factor for SLE initiation, but a temporal association with flare-ups has been described and the subject is still a matter of debate. Our systems biology approach to study pediatric autoimmune diseases has permitted us to discover novel pathways that can be applied to the study of humoral immune responses in healthy individuals. We now propose to use the same approach to study the response to influenza vaccination in healthy children and children with systemic autoimmunity. We propose to focus on 1) three cellular compartments that are essential for the generation and the quality of antibody responses to vaccine, i) the inducers (dendritic cells); ii) the regulators (CD4-i-, including follicular helper T cells), and iii) the effectors (B cells); 2) two diseases (SLE and JDM) where we have found alterations in these 3 compartments. The studies that we herein propose will address: 1) which are the best biomarkers of protective immune response to influenza vaccine in healthy children; 2) how unique autoimmune backgrounds set the stage for responsiveness/unresponsiveness to vaccines; 3) whether vaccination contributes to increase the breadth of autoimmunity in a disease-specific manner. Ultimately, we expect that these studies will shed light on basic aspects of humoral immune responses to vaccines and will permit us to discover biomarkers of response that can be applied to healthy children and to the general population.

目前的流感疫苗被认为对一般人群是安全有效的，但接种后 在先前健康的个体中已经描述了包括自身免疫性表现在内的不良事件。 尽管感染，包括流感，可以触发耀斑患者的自身免疫性疾病，无论是否 为这些患者接种疫苗仍然是一个讨论的话题。在成人系统性红斑狼疮患者中 (SLE)，据报道，流感疫苗对静止期疾病患者是安全的，但不推荐使用。 对于患有活动性疾病的患者。接种疫苗不被认为是SLE发病的原因，但 已经描述了与突发事件的时间关联，这一主题仍然是一个有争议的问题。我们的系统 研究儿科自身免疫性疾病的生物学方法使我们能够发现新的途径， 可应用于健康个体的体液免疫应答的研究。我们现在建议使用相同的 研究健康儿童和全身性疾病儿童对流感疫苗接种反应的方法 自身免疫我们建议集中在1）三个细胞隔室，这是必不可少的一代， 对疫苗的抗体应答的质量，i）诱导剂（树突状细胞）; ii）调节剂（CD 4-i-，包括 滤泡辅助T细胞），和iii）效应细胞（B细胞）; 2）两种疾病（SLE和JDM），我们发现 这三个隔间的变化。我们在此提出的研究将解决：1）哪些是最好的 健康儿童对流感疫苗的保护性免疫反应的生物标志物; 2）独特的自身免疫性 背景为疫苗的反应性/无反应性奠定了基础; 3）疫苗接种是否有助于 以疾病特异性方式增加自身免疫的广度。最终，我们希望这些研究 将阐明疫苗的体液免疫反应的基本方面，并使我们能够发现 这些生物标志物可以应用于健康儿童和一般人群。