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: 10670058
• 负责人: Jeffrey M Wilson
• 金额: $ 20.19万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670058
• 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; Categories; Clinic; Clinical; Communities; Consumption; Coronary Arteriosclerosis; Coupled; Dairying; Diagnosis; Diet; Disease; Frequencies; Future; 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; Mammals; 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; biobank; care seeking; cohort; comorbidity; galactosyl-(1-3)galactose; gastrointestinal; gastrointestinal symptom; high risk; improved; metabolomics; microbiome; novel; novel therapeutic intervention; participant enrollment; 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.

摘要 一种对哺乳动物肉类发生迟发过敏反应的综合征，现在通常称为α-Gal综合征 (AGS)2009年在美国东南部的一群病例中首次报告。将反应 与非灵长类抗原寡糖半乳糖-α-1，3-半乳糖（α-Gal）的IgE抗体相关 哺乳动物，其是健康人中IgM、IgG和伊加抗体的靶标。在过去的十年里， 越来越清楚的是，蜱叮咬，特别是来自孤独的星星蜱（美洲钝眼蜱）的叮咬， 是IgE对α-Gal致敏的主要原因，AGS病例并不罕见，也不限于小 美国的地理区域。AGS主要基于过敏症诊所调查的病例， 据了解，在摄入哺乳动物肉后3-6小时， 还报告伴随胃肠道（GI）症状的患者。然而，我们和其他人越来越多地 我们地区的提供者认识到对α-Gal敏感的患者报告孤立的GI症状， 是由哺乳动物的肉和奶制品引发的。我们也看到许多α-Gal致敏的患者携带α-Gal。 诊断为肠易激综合征（IBS），但对不含哺乳动物的饮食有良好反应的患者 肉类和奶制品。这些观察结果，加上α-Gal sIgE的人群患病率 在东南部的许多地区，敏感度超过15%，这就提出了AGS是否可以成为一种 重要和未被认识的原因IBS样介绍在我们地区。该提案的目的是进一步 调查这种可能性，并寻求更好地了解生物因素， α-Gal致敏受试者将出现重度速发型过敏反应、更轻度的IBS谱GI主诉，或 有些病例没有任何症状识别这些生物因素可能会影响AGS管理 通过改进风险分层的工具，并开辟新的治疗策略。实现 研究目标我们将开展一项以人群为基础的研究，重点关注预期高风险的受试者， α-Gal致敏风险。与大多数其他选择性招募患者的AGS研究相反， 在这里，我们将从社区招募最近被蜱虫叮咬的受试者， 而不考虑他们的过敏史。这种方法将有助于解决有关频率的公开问题， 在对α-Gal敏感的患者中出现AGS。这些疾病的临床和免疫学特征 受试者将与在我们的变态反应诊所寻求治疗的AGS患者的特征进行比较。我们还将 使用一种新的定量免疫测定来解决这样的想法， AGS表现为抗α-Gal IgG或伊加抗体相对水平较高。