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 对哺乳动物肉类的迟发性过敏反应综合征，现在通常称为 α-Gal 综合征 (AGS)，于 2009 年在美国东南部的一系列病例中首次报道。 与寡糖半乳糖-α-1,3-半乳糖 (α-Gal)（一种非灵长类抗原）的 IgE 抗体相关 哺乳动物是健康人类 IgM、IgG 和 IgA 抗体的目标，在过去的十年里。 越来越清楚的是蜱虫叮咬，特别是孤星蜱虫（Amblyomma americanum）的叮咬， 是 IgE 对 α-Gal 敏感的主要原因，AGS 病例并不罕见，也不限于小规模病例 AGS 主要基于过敏诊所调查的病例。 据了解，在摄入哺乳动物肉后 3-6 小时内会出现荨麻疹和/或过敏反应，其中许多 然而，我们和其他人越来越多地报告伴随的胃肠道 (GI) 症状。 我们地区的医疗服务提供者认识到对 α-Gal 敏感的患者，他们报告了孤立的胃肠道症状，这些症状 是由哺乳动物肉类和乳制品引发的。我们还看到许多携带 α-Gal 过敏的患者。 诊断为肠易激综合症 (IBS)，但对不含哺乳动物的饮食反应良好 这些观察结果加上 α-Gal sIgE 的人群患病率这一事实。 东南部许多地区的敏感度高达 15% 以上，提出了 AGS 是否可以成为一个问题 我们地区出现类似 IBS 的重要且未被认识的原因。该提案的目标是进一步推进。 研究这种可能性，并寻求更好地了解影响是否存在的生物因素 α-Gal 过敏的受试者会出现严重的过敏反应，更轻微的 IBS 谱胃肠道症状，或者， 在某些情况下，即使没有任何症状，此类生物因素的识别也可能会影响 AGS 管理。 通过改进风险分层工具并开辟新的治疗策略来实现这一目标。 研究目标 我们将开展一项以人群为基础的研究，重点关注预计具有高水平的主题 与大多数其他 AGS 研究不同的是，这些研究选择性地招募了患者。 曾就诊于过敏诊所的受试者，我们将从社区中招募最近被蜱虫叮咬的受试者 不考虑他们的过敏史，这种方法将有助于解决有关频率和过敏史的悬而未决的问题。 对 α-Gal 敏感的患者出现 AGS 的临床和免疫学特征。 我们还将将受试者与在我们的过敏诊所寻求治疗的 AGS 患者的特征进行比较。 采用一种新颖的定量免疫测定来解决病情不太严重的患者的想法 AGS的表现有较高相对水平的抗α-Gal IgG或IgA抗体。