Immunological Basis of Anti-IgE Therapy

描述：(研究人员摘要)：最近，一种基于抗IgE的疗法 抗体已经由制药公司开发出来。这一机制 这种疗法的有益效果的潜在原因尚不完全清楚， 但很可能与IgE水平明显下降有关。值得注意的是 是伴随的IgE-抗-IgE复合体在血清中的蓄积。另一个 治疗效果显著的是显著降低了患者的 嗜碱性粒细胞Fcepsilon RI水平。现有的文献表明， IgE水平的降低可能会导致另一种 具有免疫调节功能的Ige受体FcepsilonRII/CD23， 这表明这种疗法可能会导致免疫的其他变化。 系统。我们建议进行抗IgE治疗的机制研究 与旨在评估疗效的多中心临床试验相结合 该疗法在预防花生超敏反应中的作用。具体目标 建议的研究包括： I.抗IgE治疗对FcepsilonRI表达的影响 和嗜碱性细胞反应。我们将首先确认，抗IgE治疗会导致 降低嗜碱性粒细胞FcepsilonRI水平，然后分析这是否 发生在转录水平上。我们将确认这种疗法会导致 FcepsilonRI的交联性降低嗜碱性粒细胞的反应 确定它是否也影响非IgE刺激诱导的嗜碱性细胞反应。 治疗对皮肤肥大细胞FcepsilonRI水平的影响 调查过了。 2.抗IgE治疗对FcepsilonRII表达的影响 和抗原呈递。我们将确定这种疗法是否会导致 FcepsilonRII/CD23下调B细胞。因为展示了 该受体在抗原提呈中的作用，我们将确定 抗-IgE治疗组和对照组B细胞的抗原提呈。 3.检测抗IgE治疗对抗体产生的影响。我们 将决定抗IgE治疗是否会抑制IgE 生产，除了隔离免疫球蛋白E。IgE-抗-IgE复合体 在体外直接抑制B细胞产生IgE将被研究。这个 治疗对变态反应原激发的免疫球蛋白抗体应答的影响 也要接受评估。 我们希望所获得的知识将提高我们对抗-IgE的理解 并对这一疗法的未来发展有所裨益。我们也希望 研究将有助于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.