Novel Roles of IgE Glycosylation in Anaphylaxis

IgE 糖基化在过敏反应中的新作用

基本信息

批准号：
10543147
负责人：
Robert McCullough Anthony
金额：
$ 49.72万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10543147
关键词：
Ablation Affect Affinity Allergens Allergic Allergic Disease Allergic inflammation Anaphylaxis Anti-Inflammatory Agents Antibodies Antigens Asparagine Attenuated Basophils Binding Biological Markers Biology Biophysics Cell Count Cells Cellular Immunology Clinical Data Development Disease Epitopes Excision Food Gene Expression Glycobiology Glycoengineering Goals Human Hypersensitivity IgE IgE Receptors IgG Receptors Immune response Immunoglobulin G Immunology Individual Inflammation Insect Proteins Knowledge Lectin Link Location Mannose Mannosidase Maps Mediating Mediator Mission Modification Molecular Immunology Outcome Pathogenicity Pathway interactions Pattern Play Polysaccharides Population Positioning Attribute Post-Translational Protein Processing Public Health Regulation Research Role Sialic Acids Signal Pathway Signal Transduction Site Structure Symptoms Systemic Lupus Erythematosus Testing United States National Institutes of Health anti-IgE biomarker discovery crosslink glycosylation helminth infection in vivo innovation mast cell monomer new therapeutic target novel novel marker novel therapeutic intervention novel therapeutics prevent receptor binding sialylation sugar translational impact

项目摘要

Project Summary/Abstract. It is not clear why some individuals with allergen-specific IgE suffer from allergies, while others do not. It is likely that multiple factors contribute, including differences in IgE affinity or epitope diversity for allergens, mast cell numbers, FcεRI expression levels, Syk signaling, allergen-specific IgG antibodies, and anti-IgE antibodies. An addition factor that has not been considered is the contribution of glycosylation to IgE. Our long-term goal is to understand how glycosylation of antibodies regulates, and is regulated, by immune responses. Our central hypothesis is that IgE effector function is regulated differentially by defined glycans at distinct positions. Indeed, this is supported by preliminary data shown in this application. The rationale that underlies the proposed research is that understanding the contribution of specific IgE glycans to allergic inflammation will enable new and innovative allergic therapies. We will test our central hypothesis and, thereby, attain the objective of this application by pursuing the following three specific aims: 1) Define the IgE glycan requirements for FcεRI binding; 2) Determine how sialic acid regulates IgE-mediated anaphylaxis; 3) Examine the regulation of IgE glycosylation in vivo. Using an approach that combines biophysics, cellular and molecular immunology, and glycobiology, we will determine glycans a essential for IgE-FcεRI interactions, define a novel anti-anaphylactic pathway, establish pathogenic IgE glycosylation patterns, and attenuate anaphylaxis by modulating IgE glycans. In addition to enabling discovery of biomarkers marking allergy-causing IgE, the studies here will potentially result in identification of novel therapeutic targets for allergic disease. Finally, these studies will have impact beyond allergy in diseases in which IgE is involved, including systemic lupus erythematosus (SLE) and helminth infection. !

项目摘要/摘要。目前尚不清楚为什么一些携带过敏原特异性 IgE 的人会出现过敏，而另一些人却不会。可能有多种因素造成，包括 IgE 亲和力或过敏原表位多样性的差异、肥大细胞数量、FcεRI 表达水平、Syk 信号传导、过敏原特异性 IgG 抗体和抗 IgE 抗体。另一个尚未考虑的因素是糖基化对 IgE 的贡献，我们的长期目标是。了解抗体的糖基化如何调节免疫反应以及如何被免疫反应调节。假设是 IgE 效应子功能受到不同位置的特定聚糖的差异调节。事实上，本申请中显示的初步数据支持了这一点。拟议的研究是，了解特定 IgE 聚糖对过敏性炎症的贡献将有助于我们将测试我们的中心假设，从而实现新的和创新的过敏疗法。本申请的目标是实现以下三个具体目标：1) 定义 IgE 聚糖 FcεRI 结合的要求；2) 确定唾液酸如何调节 IgE 介导的过敏反应；3) 检查使用结合生物物理学、细胞和分子的方法来调节体内 IgE 糖基化。免疫学和糖生物学，我们将确定 IgE-FcεRI 相互作用所必需的聚糖，定义一种新的聚糖抗过敏途径，建立致病性 IgE 糖基化模式，并通过以下方式减轻过敏反应调节 IgE 聚糖除了能够发现标记引起过敏的 IgE 的生物标志物之外，这里的研究可能会确定过敏性疾病的新治疗靶点。研究将对 IgE 相关疾病（包括系统性狼疮）产生超越过敏的影响红斑狼疮（SLE）和蠕虫感染。！

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sialylation of IgE does not impact its interaction with FcεRI.

IgE 的唾液酸化不会影响其与 FcγRI 的相互作用。

DOI：
10.1111/all.16014
发表时间：
2024
期刊：
Allergy
影响因子：
12.4
作者：
Banerjee,Sayantan;Phelan,ColleenP;Reese,BrianB;Conroy,MichelleE;Anthony,RobertM
通讯作者：
Anthony,RobertM