Investigation of Immune Status and Function in Children with CNS Tumors

该建议的中心假设是NF-1患者改变了免疫系统并激活了慢性炎症途径。NF-1的存在和先天免疫系统的差异显著增加了肿瘤形成的风险。此外，我们假设免疫系统的变异是OPG异质性自然历史的原因。研究策略：文献中没有关于NF-1患儿免疫系统及其功能的现有数据。在这项研究中，我们将生成炎症和免疫循环标志物的初始数据，以表征先天免疫系统，并测试该人群和适当对照的免疫功能。我们将测量受试者循环血液中的循环细胞因子、炎症标志物和免疫系统成分。NF-1患者、NF-1合并OPG患者和无NF-1合并OPG的患者将与其未受影响的兄弟姐妹进行比较，并相互比较。方法：采集血液（以体重为限）和尿液，分析血清细胞因子、炎症和免疫介质。ELISA和Multiplex技术都将用于检测一组循环细胞因子和炎症标志物。将进行免疫表型和功能分析。中枢神经系统中的免疫反应不是均匀的，并根据释放的效应分子及其细胞和信号特异性而变化。我们假设，由于树突状细胞的激活和信号传导不足导致抗肿瘤免疫反应不足，患有NF-1的OPGs儿童对肿瘤抗原产生了耐受性。患有NF-1的儿童发生神经胶质瘤的几率增加，其中最常见的是视神经通路和下丘脑。在小鼠和人类视神经胶质瘤中大量存在的小胶质细胞通过产生前列腺素和促炎细胞因子对刺激作出反应组织损伤、免疫系统激活或炎症反应会产生许多不同的细胞因子，细胞和组织对细胞因子的反应取决于每个细胞上受体的存在和数量。我们将采集血液，测量免疫球蛋白水平和肥大细胞数量。此外，将使用ELISA和Mesoplex技术测量midkine，血浆组胺和血清SCF。由于这是一项新的研究，我们目前正在确定潜在的参与者并收集样本进行分析。

The central hypothesis of this proposal is that patients with NF-1 have altered immune systems and activation of chronic inflammation pathways. The presence of NF-1 together with differences in the innate immune system significantly increases the risk of tumor formation. In addition, we hypothesize that variations in the immune system are responsible for the heterogeneous natural history of OPG. Research Strategy: There is no existing data in the literature on the immune system or its function in children with NF-1. In this study, we will generate initial data on circulating markers of inflammation and immunity, to characterize the innate immune system, and to test immune function in this population and appropriate controls. We will measure circulating cytokines, inflammatory markers and components of the immune system in circulating blood of subjects. Patients with NF-1, patients with NF-1 and OPG, and patients without NF-1 who have OPGs will be compared to their unaffected siblings and to each other. Methods: Blood (amount limited by body weight) and urine will be collected for analysis of serum cytokines, inflammation and immune mediators. Both ELISA and Multiplex technologies will be used to assay a panel of circulating cytokines and inflammatory markers. Immunophenotyping and functional assays will be performed. The immune response in the CNS is not homogeneous, and varies depending on the effector molecules released and their cell and signal specificities.We hypothesize that children with NF-1 who develop OPGs have developed tolerance to tumor antigens due to deficient activation and signaling of dendritic cells resulting in an inadequate antitumor immune response. Children with NF-1 have an increased incidence of gliomas, which most frequently involve the optic pathway and hypothalamus. Microglia, which are abundant in mouse and human optic pathway gliomas, respond to stimuli by producing prostaglandins and pro-inflammatory cytokines.2 A number of different cytokines are produced in response to tissue damage, activation of the immune system or the inflammatory response, and the cell and tissue response to cytokines depends upon the presence and number of receptors on each cell. We will collect blood for measurement of immunoglobulin levels and mast cell numbers. In addition, midkine, plasma histamine and serum SCF will be measured using ELISA and Mesoplex technologies. As this is a new study, we are currently in the process of identifying potential participants and collecting samples for analyses.