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%的澳大利亚人。它是造成重大疾病和死亡的原因，特别是在儿童中，其发病率正在上升。造成这种情况的原因以及过敏性疾病的潜在原因尚不清楚。过敏性疾病是由一种叫做IgE抗体的分子引起的，这种分子也与寄生虫感染有关。即使在这种情况下，血液中的IgE浓度升高，浓度也太低，无法进行直接研究。我们最近应用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反应有时会以不同于其他抗体（如IgG）的方式发展。另一方面，多年来的实验室（体外）研究支持IgE和IgG平行发展的可能性。在这项研究中，我们希望确定igg样IgE抗体产生的情况。因此，我们希望研究不同种类的过敏性疾病患者，以及与IgE产生相关的其他疾病患者。因此，我们希望研究感染寄生虫的病人。我们通过分析抗体基因在免疫反应中积累的突变模式，推断出产生IgE抗体的过程。近年来，我们已经开发了新的方法来分析这种突变，这个项目也寻求进一步发展我们的突变分析。这种更有力的分析将应用于不同患者群体中IgE基因突变的研究，并使我们能够量化每种方式产生的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，并为研究过敏性疾病的原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.