Novel Roles of IgE Glycosylation in Anaphylaxis

IgE 糖基化在过敏反应中的新作用

• 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
• 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

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。 尚不清楚为什么有些患有特异性IGE的人患有过敏，而另一些人则没有。这是 多种因素可能会导致多种因素，包括过敏原的IgE亲和力或表位多样性的差异，桅杆 细胞数，FcεRI表达水平，SYK信号传导，过敏原特异性IgG抗体和抗IgE抗体。 尚未考虑的添加因素是糖基化对IgE的贡献。我们的长期目标是 了解抗体的糖基化如何通过免疫反应调节并受到调节。我们的中心 假设是，在不同位置处的定义的聚糖对IgE效应函数进行了不同的调节。 确实，这是由本应用程序中显示的初步数据支持的。基于 拟议的研究是，了解特定的IgE聚糖对过敏性注射的贡献 启用新的和创新的过敏疗法。我们将检验我们的中心假设，从而获得 通过追求以下三个特定目的来实现本应用的目的：1）定义IgE Glycan 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 体内IgE糖基化的调节。使用结合生物物理学，细胞和分子的方法 免疫学和糖生物学，我们将确定Glycans对IgE-FcεRI相互作用的必不可少的，它定义了一种新颖 抗侵犯性途径，建立致病性IgE糖基化模式，并通过 调节IgE糖。除了能够发现标记引起过敏IgE的生物标志物， 这里的研究可能会导致确定过敏性疾病的新治疗靶标。最后，这些 研究将在涉及IgE的疾病中产生影响，包括全身性狼疮 红斑（SLE）和蠕虫感染。 呢

项目成果

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