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

通过体细胞点突变分析鉴定人类 IgE 反应中的抗原选择

• 批准号: nhmrc : 455440
• 负责人: A/Pr Andrew Collins
• 金额: $ 17.13万
• 依托单位: The University of New South Wales
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/identification-antigen-selection-point-mutations/96588
• 关键词: Identification; antigen; selection; human; IgE

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.

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。其原因以及过敏性疾病的根本原因尚不清楚。过敏性疾病是由称为IgE抗体的分子的作用引起的，IgE抗体也与寄生虫感染有关。即使在这些条件下，IgE浓度在血液中升高，浓度太低，不允许直接研究。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反应有时可以以与其他抗体（例如IgG）不同的方式发生。另一方面，多年的实验室（体外）研究支持IgE和IgG平行发展的可能性。在这项研究中，我们希望确定的情况下，IgG样IgE抗体的发展。因此，我们希望研究患有不同类型过敏性疾病的患者，以及患有与IgE产生相关的其他疾病的患者。因此，我们希望研究寄生蠕虫的患者。我们通过分析在免疫应答过程中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，我们开发了新的方法来分析这种突变，这个项目也试图进一步发展我们的突变分析。这种更强大的分析将应用于研究不同患者群体中IgE基因的突变，并应使我们能够量化以每种方式产生的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病因和治疗开辟新的途径。