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于了解 对主要血型低聚糖-1，3-半乳糖(？-GAL)的免疫应答 非灵长类哺乳动物的物质。这些研究主要集中在三个方面。(I)了解 进食后迟发性变态反应的流行病学及临床处理 被称为？-半乳糖综合征(AGS)的哺乳动物产品。而证候明显 与孤星扁虱的分布有关，有越来越多的证据表明 火蚁可能会干扰南方的这种扁虱，而且这种扁虱的活动范围正在向北移动 美国。我们计划使用检测方法来识别食品和医药产品中的β-半乳糖表位，例如CroFab 还有肝素。有许多这样的物品与哺乳动物的原始材料和 可能被污染了。(2)对与AGS有关的血清学和细胞反应进行全面调查 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 与AGS相关的免疫反应和细胞反应的基础 光谱流分析技术。此外，我们建议把这些研究扩展至与 其他形式的食物过敏，特别是嗜酸性食管炎，像AGS一样，只成为 在过去的30年里很常见，但在免疫学和临床上完全不同。(三)详细说明 两种情况下IgE转β-GAL患者出现腹部症状或 没有任何通常被认为是过敏的症状的冠心病。关于以下方面的证据 这两个条件都是最近发展起来的。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。更有甚者 弗吉尼亚州冠状动脉造影术患者循环中B细胞的调查 提供了支持B细胞与β-GAL心脏风险的相关性的证据。腹部病例 也构成了美国地区肠易激综合征(IBS)病例的主要百分比 被孤星扁虱叮咬的地方很常见，例如弗吉尼亚州中部。我们的计划是在 这些猪肉使用？-GAL敲除猪肉作为盲目安慰剂的情况下进一步调查 为这种关联提供证据，并进一步了解红肉的延迟临床反应。

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.