IgE antibodies to the mammalian oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal): immunology, epidemiology and relevance to allergic and inflammatory disease

我们正在进行的和拟议的研究集中在了解的原因和后果的 IgE对寡糖半乳糖α-1，3-半乳糖（？gal）是一种主要的血型 非灵长类哺乳动物的物质。这些研究集中在三个领域。(i)了解 食后迟发性过敏反应的流行病学和临床管理 哺乳动物产品，被称为？半乳糖综合征（AGS）。虽然这种综合症 与孤星星蜱Amblyomma americanum的分布有关，越来越多的证据表明， 火蚁可以在南方干扰这种蜱虫，而且这种蜱虫的范围正在向北移动， 美国.我们计划用化验来鉴定？-食品和药品中的gal表位，例如CroFab 和肝素。有许多这样的项目，有一些连接到哺乳动物源材料， 可能被污染了(ii)与AGS相关的血清学和细胞应答的全面研究 包括与其他形式的食物过敏的比较。这些研究将继续调查细胞 使用最近开发的免疫应答和与AGS相关的细胞应答， 频谱流分析技术此外，我们建议将这些研究扩展到与 其他形式的食物过敏，特别是嗜酸性食管炎，像AGS一样， 在过去的30年里很常见，但在免疫学和临床上完全不同。(iii)详细 研究了两种情况，病人的IgE到哪里去了？gal出现腹部症状或 冠状动脉疾病，没有任何症状，通常被认为是过敏。的证据 这两种情况是最近才出现的。与心脏风险的关系于2018年首次报道 最近在澳大利亚悉尼举行的心脏病学会议上也报告了类似的数据。此外 对弗吉尼亚州接受冠状动脉造影术的患者循环中的B细胞进行了一项调查， 提供了支持B细胞与？-加腹部病例 在美国的一些地区，肠易激综合征（IBS）病例中也占很大比例 在弗吉尼亚州中部等地，孤独的星星蜱叮咬很常见。我们的计划是在 这些猪肉案件使用？gal敲除猪肉作为盲法安慰剂，以进一步研究 研究表明，红肉的延迟临床反应可能是一个潜在的证据，并进一步了解红肉延迟临床反应。

Our ongoing and proposed studies are focused on understanding the causes and consequences of the IgE response to the oligosaccharide galactose alpha-1,3-galactose (?-gal) which is a major blood group substance of non-primate mammals. These studies are focused on three areas. (i) Understanding the epidemiology and clinical management of the delayed allergic reactions that occur after eating mammalian products which are referred to as the ?-gal syndrome (AGS). While the syndrome clearly relates to the distribution of the lone star ticks, Amblyomma americanum, there is increasing evidence that fire ants can interfere with this tick in the south and also that the range of this tick is moving northwards in the USA. We plan to use assays to identify the ?-gal epitope in food and medicinal products, e.g. CroFab and heparin. There are many such items that have some connection to mammalian source materials and could be contaminated. (ii) Full investigation of the serology and cellular responses related to AGS including comparison with other forms of food allergy. These studies will continue investigating the cellular basis of the immune response and cellular responses related to AGS using recent development of the technique of spectral flow analysis. In addition, we propose to extend these studies to a comparison with other forms of food allergy in particular with Eosinophilic Esophagitis, which like AGS has only become common over the last 30 years but is immunologically and clinically completely different. (iii) Detailed studies on two situations, where patients with IgE to ?-gal develop either abdominal symptoms or coronary artery disease without any symptoms that are typically regarded as allergic. Evidence about these two conditions has developed recently. The relationship to cardiac risk was first reported in 2018 and similar data has recently been reported to a cardiology meeting in Sydney, Australia. Furthermore investigation of B cells in the circulation of patients undergoing coronary angiography in Virginia has provided evidence supporting the relevance of B cells to the cardiac risk of ?-gal. The abdominal cases also make up a major percentage of the cases of irritable bowel syndrome (IBS) in areas of the USA where bites from the lone star tick are common e.g. Central Virginia. Our plan is to carry out challenges in these cases with pork meat using ?-gal knock-out pork as a blinded placebo to further investigate the evidence for the association and to further understand the delayed clinical reactions to red meat.