THE HYPEREOSINOPHILIC SYNDROMES AND MEPOLIZUMAB

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Mepolizumab是一种高亲和力、特异性、人源化的IL-5单克隆抗体，可快速清除外周血中的嗜酸性粒细胞。这种抗体已被用于几种疾病的患者，包括哮喘，并且它明显没有副作用；安慰剂组和治疗组是无法区分的。在一项研究中，mepolizumab对少数嗜酸性粒细胞增多综合征（HES）患者的治疗显著地使他们受益，并且这种治疗可能减少了HES和嗜酸性粒细胞增多性皮炎患者潜在的辅助性T 2 （Th2）优势。mepolizumab治疗HES的多中心临床试验正在进行中，以实现三个目标：1。确定mepolizumab是否调节t细胞的功能，包括分化和细胞因子的产生2。检测mepolizumab治疗是否抑制治疗患者嗜酸性粒细胞活化及嗜酸性粒细胞IL-5受体的表达确定mepolizumab是否显示先前未发现的HES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