THE HYPEREOSINOPHILIC SYNDROMES AND MEPOLIZUMAB

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。美波利单抗是一种抗IL-5的高亲和力、特异性、人源化的单抗，能迅速清除外周血中的嗜酸性粒细胞。这种抗体已经用于包括哮喘在内的几种疾病的患者，而且它非常没有副作用；安慰剂组和治疗组没有区别。甲波利单抗对少数高嗜酸粒细胞综合征(HES)患者有显著的益处，在一项研究中，这种治疗可能降低了HES和嗜酸性皮炎患者潜在的T辅助细胞(Th2)优势。一项治疗HES的多中心临床试验正在进行中，目的有三：1.确定美波利单抗是否调节T细胞的功能，包括分化和细胞因子的产生；2.测试美波利单抗治疗是否抑制嗜酸性粒细胞的激活和嗜酸性粒细胞上IL-5受体的表达3.确定美波利单抗是否表现出以前未发现的HES的异质性

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mepolizumab is a high-affinity, specific, humanized monoclonal antibody to IL-5 which rapidly depletes eosinophils from the peripheral blood. This antibody has been administered to patients with several diseases, including asthma, and it is remarkably free of side-effects; the placebo and treatment groups are indistinguishable. Administration of mepolizumab to a few patients with hypereosinophilic syndrome (HES) has dramatically benefited them, and in one study this treatment may have lessened the underlying T helper 2 (Th2) predominance in patients with HES and eosinophilic dermatitis. A multicenter clinical trial of mepolizumab for the treatment of HES is underway to address three aims: 1. Determine if mepolizumab modulates the functions of T-cells, including differentiation and cytokine production 2. Test whether mepolizumab treatment suppresses eosinophil activation and expression of the IL-5 receptor on eosinophils of treated patients 3. Determine if mepolizumab reveals heterogeneity in HES not previously recognized