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

摘要 对哺乳动物肉类迟发性过敏的综合征，现在通常被称为α-Gal型综合征 (AGS)于2009年在美国东南部的一系列病例中首次报告。他们的反应是 与非灵长类动物抗原低聚半乳糖-α-1，3-半乳糖(α-Gal)抗体相关 哺乳动物是健康人类免疫球蛋白M、免疫球蛋白和免疫球蛋白A抗体的靶标。在过去的十年里，它 越来越清楚的是，扁虱的叮咬，特别是来自独星扁虱(Amblyomma Americanum)的叮咬， 是α-GalIg E致敏的主要原因，AGS病例并不罕见，也不局限于小病例 美国的地理区域。主要基于过敏症诊所调查的病例，AGS是 据了解，在摄入哺乳动物肉类3-6小时后表现为麻疹和/或过敏反应，许多 患者还报告了伴随的胃肠道(GI)症状。然而，我们和其他人越来越多地 我们地区的供应商认可对α-Gal敏感的患者，这些患者报告了单独的胃肠道症状， 是由哺乳动物的肉类和乳制品引发的。我们还看到许多α-Gal型致敏患者携带 诊断为肠易激综合征(IBS)，但对不含哺乳动物的饮食反应良好 肉类和乳制品。这些观察结果，再加上α-GalsIgE的人群流行率 在东南部的许多地区，敏感率超过15%，这引发了AGS是否可能是一种 在我们地区出现IBS样表现的重要和未被认识到的原因。这项提议的目标是进一步 调查这种可能性，并寻求更好地了解影响 α-Gal致敏的受试者将出现严重的过敏反应，较轻微的肠易激综合征谱GI症状，或 有些病例，没有任何症状。认识到这些生物因素可能会影响AGS的管理 通过改进风险分层工具和开辟新的治疗策略。要实现 研究目标我们将开展一项以人群为基础的研究，重点关注预计高- α-Gal致敏的风险。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 在这里，我们将从社区招募最近被虱子叮咬的受试者 而不考虑他们的过敏史。这种方法将有助于解决有关频率和 在对α-Gal敏感的人中介绍AGs。这些疾病的临床和免疫学特征 受试者将与在我们过敏诊所寻求治疗的AGS患者的特征进行比较。我们还将 使用一种新的定量免疫分析来解决这种想法，即那些病情较轻的患者 AGS表现为抗α-GalIg G或Ig A抗体相对水平较高。

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.