Investigation of the prevalence, presentation and immunologic features of the α-Gal syndrome in a high-risk cohort not recruited on the basis of allergic disease

未根据过敏性疾病招募的高危人群中 α-Gal 综合征的患病率、表现和免疫学特征的调查

• 批准号: 10353468
• 负责人: Jeffrey M Wilson
• 金额: $ 24.23万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-22 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10353468
• 关键词: Address; Adult; Affect; Allergic; Allergic Disease; Amblyomma; Ambylomma americanum; Anaphylaxis; Antibodies; Antigens; Area; Awareness; Basophils; Biological Assay; Biological Factors; Biological Markers; Bite; Blood specimen; Clinic; Clinical; Communities; Consumption; Coronary Arteriosclerosis; Coupled; Diagnosis; Diet; Disease; Enrollment; Frequencies; Future; Galactose; Geographic Locations; Glycoproteins; Goals; Heterogeneity; Hour; Human; Hypersensitivity; IgE; IgG4; Immediate hypersensitivity; Immunoassay; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Factors; Immunologics; Immunology; In Vitro; Individual; Ingestion; Investigation; Irritable Bowel Syndrome; Knowledge; Link; Meat; Mediating; Medical; Nature; Oligosaccharides; Participant; Patients; Phenotype; Plasma; Population; Population Study; Prevalence; Provider; Questionnaires; Reaction; Recording of previous events; Reporting; Saliva; Sampling; Secretory Immunoglobulin A; Serum; Severities; Southeastern United States; Symptoms; Syndrome; Testing; Thinking; Ticks; United States; Urine; Urticaria; Variant; Virginia; alpha-gal syndrome; antibody test; base; care seeking; cohort; comorbidity; gastrointestinal; gastrointestinal symptom; high risk; improved; metabolomics; microbiome; novel; novel therapeutic intervention; protective effect; recruit; risk stratification; saliva sample; seropositive; stool sample; tick bite; tool

ABSTRACT A syndrome of delayed anaphylaxis to mammalian meat, now commonly referred to as the α-Gal syndrome (AGS), was first reported in 2009 in a cluster of cases in the southeastern United States. The reactions were related to IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (α-Gal), an antigen of non-primate mammals which is the target of IgM, IgG and IgA antibodies in healthy humans. Over the past ten years it has become increasingly clear that tick bites, particularly bites from the lone star tick (Amblyomma americanum), are the dominant cause of IgE sensitization to α-Gal and that AGS cases are not rare, nor limited to small geographic areas of the United States. Based largely on cases investigated in allergy clinics, AGS is understood to manifest with hives and/or anaphylaxis 3-6 hours after ingestion of mammalian meat, with many patients also reporting concomitant gastrointestinal (GI) symptoms. Increasingly, however, we and other providers in our area recognize patients who are sensitized to α-Gal that report isolated GI symptoms which are triggered by mammalian meat and dairy. We are also seeing many α-Gal sensitized patients who carry a diagnosis of irritable bowel syndrome (IBS), but who have responded favorably to a diet free of mammalian meat and dairy. These observations, coupled with the fact that the population prevalence of α-Gal sIgE sensitization is upwards of 15% in many parts of the Southeast, raise the question of whether AGS could be an important and unrecognized cause of IBS-like presentations in our region. The goal of this proposal is to further investigate this possibility and also to seek a better understanding of the biological factors that affect whether an α-Gal sensitized subject will present with severe anaphylaxis, more mild IBS-spectrum GI complaints or, in some cases, no symptoms whatsoever. Recognition of such biological factors could impact AGS management by leading to improved tools for risk stratification and open up novel therapeutic strategies. To achieve the study objectives we will carry out a population-based study focusing on subjects that are expected to be high- risk for α-Gal sensitization. In contrast to most other studies of AGS, which have selectively enrolled patients who have presented to allergy clinics, here we will recruit subjects with recent tick bites from the community without regard to their allergic history. This approach will help address open questions about the frequency and presentation of AGS among those who are sensitized to α-Gal. Clinical and immunologic features of these subjects will be compared with features of AGS patients who seek care in our allergy clinic. We will also employ a novel quantitative immunoassay to address the idea that patients who have less severe manifestations of AGS have higher relative levels of anti-α-Gal IgG or IgA antibodies.

抽象的 延迟过敏症综合征对哺乳动物肉，现在通常称为α-gal综合征 （AGS）于2009年首次报道了美国东南部的一系列病例。反应是 与寡糖半乳糖-α-1,3-半乳糖（α-gal）的IgE抗体有关，这是一种非根源的抗原 哺乳动物是健康人的IgM，IgG和IgA抗体的靶标。在过去的十年中 越来越清楚地表明，tick叮咬，尤其是孤星tick（Amblyomma Americanum）的碎屑， 是对α-gal敏感性敏感的主要原因，并且AGS病例并不罕见，也不限于小 美国的地理区域。主要基于在过敏诊所调查的病例，AGS是 了解摄入哺乳动物肉后3-6小时与蜂箱和/或过敏反应表现出来，许多 患者还报告胃肠道（GI）符号。但是，我们和其他 我们地区的提供者认识到对α-gal敏感的患者，该患者报告了孤立的胃肠道符号 由哺乳动物肉和乳制品触发。我们还看到许多携带A的α-GAL敏感患者 诊断肠易激综合症（IBS），但对不含哺乳动物的饮食的反应良好 肉和乳制品。这些观察结果以及α-gal sige的种群流行率 在东南部许多地方，致敏性高达15％，提出了一个问题，即AG是否可以成为 在我们地区，重要且无法识别的IBS样品。该提议的目的是进一步 调查这种可能性，并寻求更好地了解影响的生物学因素 α-GAL敏感受试者将出现严重的过敏反应，更轻微的IBS频谱GI投诉或在 在某些情况下，没有任何症状。对这种生物学因素的认识可能会影响AGS管理 通过改进了风险分层的工具并打开新的治疗策略。实现 研究目标我们将进行一项基于人群的研究，重点是预计会很高的受试者 α-GAL灵敏度的风险。与大多数其他AGS研究相反，AGS有选择性地招募患者 向过敏诊所展示的人，在这里，我们将招募社区最近的tick虫咬伤的主题 不考虑其过敏史。这种方法将有助于解决有关频率和 对α-gal敏感的人的AG呈现。这些的临床和免疫学特征 将受试者与在我们的过敏诊所寻求护理的AGS患者的特征进行比较。我们也会 员工是一种新颖的定量免疫测定法，以解决以下观点 AG的表现具有较高的抗α-GAL IgG或IgA抗体的相对水平。