Identification of antigen selection in the human IgE response by analysis of somatic point mutations

过敏性疾病影响了超过25%的澳大利亚社区。它是导致重大疾病和死亡的原因，特别是在儿童中，而且其发病率正在增加。造成这种情况的原因以及导致过敏性疾病的根本原因尚不清楚。过敏性疾病是由被称为IgE抗体的分子的作用引起的，这种抗体也与寄生虫感染有关。即使在这些条件下，血液中的IgE浓度会上升，但浓度太低，无法直接进行研究。我们最近应用了分子生物学技术来研究编码IgE抗体的基因。我们的工作表明，IgE反应有时可以以不同于其他抗体(如免疫球蛋白)的方式发展。另一方面，多年来的实验室(体外)研究支持免疫球蛋白E和免疫球蛋白同时发展的可能性。在这项研究中，我们希望确定在什么情况下会产生类IgE抗体。因此，我们希望研究不同类型过敏性疾病的患者，以及与IgE产生相关的其他情况的患者。因此，我们希望研究感染寄生虫的患者。我们通过分析免疫反应期间抗体基因中积累的突变模式来推断产生IgE抗体的过程。近年来，我们开发了分析此类突变的新方法，该项目也寻求进一步发展我们的突变分析。这一更强大的分析将应用于研究在不同患者群体中发现的IgE基因突变，并应使我们能够量化每种方式发展的IgE抗体的比例。更好地了解这两种途径在不同条件下对IgE的相对贡献，将改变我们对IgE反应的理解，并为过敏性疾病的病因和治疗开辟新的途径。

Allergic disease affects over 25% of the Australian community. It is responsible for significant sickness and death, particularly amongst children, and its incidence is on the increase. The reasons for this, and the underlying causes of allergic disease, remain unclear. Allergic disease results from the actions of molecules called IgE antibodies, which are also associated with parasitic infection. Even in these conditions, where IgE concentrations are raised in the blood, the concentrations are too low to allow their direct study. We have recently applied molecular biological techniques to study the genes that encode IgE antibodies. Our work suggests that the IgE response can sometimes develop in a different way to that of other antibodies (eg IgG). On the other hand, laboratory (in vitro) studies over many years support the possibility that IgE and IgG develop in parallel. In this study, we wish to identify circumstances in which IgG-like IgE antibodies develop. We therefore wish to study patients with different kinds of allergic disease, and patients with other conditions that are associated with IgE production. We therefore wish to study patients who have infections with parasitic worms. We deduce the processes that give rise to IgE antibodies by analysing patterns of mutations that accumulate in antibody genes during an immune response. Over recent years, we have developed new approaches to the analysis of such mutations, and this project also seeks to further develop our mutation analysis. This more powerful analysis will be applied to the study of mutations in the IgE genes seen in different patient groups, and should allow us to quantify the proportion of IgE antibodies that develop in each way. A better understanding of the relative contributions of the two pathways to IgE, in different conditions, will transform our understanding of the IgE response, and open up new avenues for the investigation of the causes and treatment of allergic disease.