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

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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.