Molecular Factors Involved in Tick-Bite Mediated Allergy to the Carbohydrate Alpha-Gal

Red meat allergy aka α-Gal allergy is a delayed allergic response occurring upon consumption of mammalian meat and by-products. Patients report eating meat without any problems for several years before developing the allergy. Although children can develop red meat allergy, it is more prevalent in adults. In addition to a delayed onset of reactions, immediate hypersensitivity is reported in case of contact with the allergen via intravenous route. Galactose-α-1,3-galactose (α-Gal) is the first highly allergenic carbohydrate that has been identified to cause allergy all across the world. In general, carbohydrates exhibit low immunogenicity and are not capable of inducing a strong immune response on their own. Although the α-Gal epitope is present in conjugation with both proteins and lipids, due to an overall accepted role of proteins in allergy, glycoproteins from mammalian food sources were first characterized. However, a unique feature of α-Gal allergy is the delayed occurrence of allergic symptoms upon ingestion of mammalian meat and an allergenic role of glycolipids has been proposed to explain these delayed responses.
A second important feature of the disease is that the development of specific IgE to α-Gal has been associated with tick bites belonging to various tick species, depending on the geographical region. In this tick-mediated allergy an intriguing factor is the absence of an α-1,3-GalT gene in ticks, a gene coding for an enzyme capable of α-Gal synthesis, which raises questions on the source and identity of the sensitizing molecule within ticks, immune responses to tick bites, and effect of increased exposure.
In this study, we sought to elucidate the origin of sensitization to α-Gal by investigating a cohort of individuals exposed to recurrent tick bites and by exploring the proteome of ticks in a longitudinal study. Furthermore, we analysed the allergenicity of glycoproteins and glycolipids in order to determine the food components responsible for the delayed onset of symptoms.
The aim of the Chapter I was to determine IgG profiles and the prevalence rate of sensitization to α-Gal in a high-risk cohort of forestry employees from Luxembourg.
The aim of Chapter II was to analyse the presence of host blood in Ixodes ricinus after moulting and upon prolonged starvation in order to support or reject the host blood transmission hypothesis.
The aim of the Chapter III was to investigate and compare the allergenicity of glycolipids and glycoproteins to understand their role in the allergic response. Moreover, we have analysed the stability of glycoproteins and compared extracts from different food sources. This chapter is in the form of a published article.
In Chapter IV, I have made an attempt to create mutant models with specified α-Gal glycosylation in order to study role of spatial distribution of α-Gal in IgE cross linking and effector cell activation.