Immunological Basis of Anti-IgE Therapy

描述：（研究者摘要）：最近，一种基于抗IgE的治疗 抗体已经被制药公司开发出来。机制 这种疗法的潜在有益效果还不完全清楚， 但可能与IgE水平的显著降低有关。值得注意的 是IgE-抗IgE复合物在血清中的伴随积累。另一 治疗的显著效果是大幅度减少 嗜碱性粒细胞上的Fc ε RI水平。现有文献表明， IgE水平的降低可能导致另一种免疫调节的下调。 IgE受体，Fc受体RII/CD 23，其具有免疫调节功能， 这表明该疗法可能导致免疫系统的其他改变， 系统我们建议进行抗IgE治疗的机制研究， 结合多中心临床试验，旨在评估疗效 花生过敏症的治疗方法具体目标 拟议的研究包括： I.测定抗IgE治疗对Fc ε RI表达的影响 和嗜碱性粒细胞反应。我们将首先证实抗IgE治疗会导致 降低嗜碱性粒细胞上的FceppsilonRI水平，然后分析这是否 发生在转录水平。我们将证实治疗会导致 减少嗜碱性粒细胞对Fc ε RI交联的反应，然后 确定它是否也影响由非IgE刺激诱导的嗜碱性粒细胞反应。 将研究该疗法对皮肤肥大细胞上Fc ε RI水平的影响。 研究了 2.测定抗IgE治疗对Fc ε RII表达的影响 和抗原呈递。我们将确定治疗是否会导致 下调B细胞上的Fc受体RII/CD 23。由于所展示的 该受体在抗原呈递中的功能，我们将确定 来自抗IgE治疗的受试者和对照受试者的B细胞的抗原呈递。 3.测定抗IgE治疗对抗体产生的影响。我们 将确定抗IgE治疗是否导致IgE抑制 除了IgE的螯合之外，还产生。IgE-抗IgE复合物是否 将研究体外直接抑制B细胞的IgE产生。的 治疗对IgG抗体对变应原攻击的反应的影响将 也要评估。 我们希望所获得的知识将提高我们对抗IgE的理解 有利于该疗法的进一步发展。我们也希望 研究将导致更好地了解过敏的机制， 疾病

DESCRIPTION:(Investigator's abstract): Recently, a therapy based on anti-IgE antibodies has been developed by pharmaceutical companies. The mechanism underlying the beneficial effect of this therapy is not completely understood, but is likely to be related to the marked reduction in the IgE level. Of note is the concomitant accumulation of IgE-anti-IgE complexes in the sera. Another remarkable effect of the treatment is the substantial reduction in the FcepsilonRI level on basophils. The existing literature suggests that the reduction in the IgE level is likely to result in a down-regulation of another IgE receptor, FcepsilonRII/CD23, which has an immunomodulatory function, suggesting that the therapy may result in other alterations of the immune system. We propose to conduct mechanistic studies of anti-IgE therapy in conjunction with a multicenter clinical trial designed to evaluate the efficacy of the therapy in preventing peanut-induced hypersensitivity. The specific aims of the proposed research are: I. Determination of the effect of anti-IgE therapy on FcepsilonRI expression and basophil responses. We will first confirm that anti-IgE therapy causes a reduction in the FcepsilonRI level on basophils and then analyze whether this occurs at a transcriptional level. We will confirm that the therapy causes a reduction in basophil response to cross-linkage of FcepsilonRI and then determine whether it also affects basophil response induced by non-IgE stimuli. The effect of the therapy on the FcepsilonRI level on skin mast cells will be investigated. 2. Determination of the effect of anti-IgE therapy on FcepsilonRII expression and antigen presentation. We will determine whether the therapy results in a down-regulation of FcepsilonRII/CD23 on B cells. Because of the demonstrated function of this receptor in antigen presentation, we will determine the antigen presentation by B cells from anti-IgE treated and control subjects. 3. Determination of the effect of anti-IgE therapy on antibody production. We will determine whether anti-IgE therapy results in a suppression of IgE production, in addition to sequestration of IgE. Whether IgE-anti-IgE complexes directly suppress IgE production by B cells in vitro will be investigated. The effect of the therapy on the IgG antibody response to allergen challenge will also be assessed. We hope that the knowledge obtained will improve our understanding of anti-IgE therapy and benefit future development of this therapy. We also hope that the studies will lead to a better understanding of the mechanisms of allergic diseases.