Systems Biology Approach to Study Influenza Vaccine in Children with Autoimmunity

目前的流感疫苗被认为对普通人群安全有效，但在接种疫苗后 不良事件，包括自身免疫的表现，已经在以前的健康个体中描述过。 尽管感染，包括流感，会引发自身免疫性疾病患者的症状发作，无论是否 为这些患者接种疫苗仍然是一个讨论的主题。成人系统性红斑狼疮患者的临床研究 据报道，流感疫苗对静止期患者是安全的，但不建议接种。 适用于活动性疾病患者。接种疫苗不被认为是系统性红斑狼疮发病的原因，但 与突发事件的时间联系已经被描述，这个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， 可应用于健康人体液免疫反应的研究。我们现在提议使用相同的 研究健康儿童和系统性疾病儿童对流感疫苗接种反应的方法 自身免疫力。我们建议将重点放在1)三个细胞隔间，这三个细胞隔间对于生成和 对疫苗的抗体反应的质量，一)诱导物(树突状细胞)；二)调节因子(CD4-I-，包括 滤泡辅助T细胞)，以及III)效应器(B细胞)；2)我们已经发现的两种疾病(SLE和JDM) 这3个车厢的改装。我们在这里提出的研究将解决：1)哪些是最好的 健康儿童对流感疫苗保护性免疫反应的生物标志物；2)自身免疫的独特性 背景为疫苗的应答/无应答奠定了基础；3)接种疫苗是否有助于 以疾病特异性的方式增加自身免疫的广度。最终，我们预计这些研究 将阐明对疫苗的体液免疫反应的基本方面，并将使我们能够发现 可应用于健康儿童和普通人群的反应生物标记物。

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.