T-cell and B-cell Immunology (33)Immune Cell Function and Interaction (22)Immunotherapy and Immune Responses (15)Monoclonal and Polyclonal Antibodies Research (11)Food Allergy and Anaphylaxis Research (9)
Allergology international : official journal of the Japanese Society of Allergology •
Alpha-gal syndrome (AGS) is a unique allergic condition triggered by IgE antibody production against the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal). The syndrome, acquired by bites from multiple tick species, leads to delayed allergic reactions after consuming mammalian-derived products containing α-gal, including red meat, dairy, and select medications. AGS is especially prevalent in regions with high tick exposure and has become a global public health concern, with rising cases across continents. Despite growing research, including recent findings suggesting that asymptomatic α-gal sensitization may contribute to coronary artery disease, the precise immune mechanisms-particularly B cell-mediated IgE production following tick bites-remain poorly understood. Additionally, the tick saliva components that trigger sensitization and the role of the skin-gut axis in food allergy development are knowledge gaps. AGS research has benefited from animal models like mice, zebrafish, and pigs, which replicate key syndrome features, though have limitations. Humanized mouse models and human organoid systems now offer promising tools for investigating AGS pathogenesis and testing potential therapies. This review explores current pre-clinical methodologies, challenges, and the future of AGS research, emphasizing innovative models that may bridge knowledge gaps and advance therapeutic development.
Wilson JM, Erickson L, Levin M, Ailsworth SM, Commins SP, et al.
Allergy •
The recent recognition of a syndrome of tick-acquired mammalian meat allergy has transformed the previously held view that mammalian meat is an uncommon allergen. The syndrome, mediated by IgE antibodies against the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), can also involve reactions to visceral organs, dairy, gelatin and other products, including medications sourced from non-primate mammals. Thus, fittingly, this allergic disorder is now called the alpha-gal syndrome (AGS). The syndrome is strikingly regional, reflecting the important role of tick bites in sensitization, and is more common in demographic groups at risk of tick exposure. Reactions in AGS are delayed, often by 2-6 h after ingestion of mammalian meat. In addition to classic allergic symptomatology such as urticaria and anaphylaxis, AGS is increasingly recognized as a cause of isolated gastrointestinal morbidity and alpha-gal sensitization has also been linked with cardiovascular disease. The unusual link with tick bites may be explained by the fact that allergic cells and mediators are mobilized to the site of tick bites and play a role in resistance against ticks and tick-borne infections. IgE directed to alpha-gal is likely an incidental consequence of what is otherwise an adaptive immune strategy for host defense against endo- and ectoparasites, including ticks.
Saunders MN, Rival CM, Mandal M, Cramton K, Rad LM, et al.
Frontiers in allergy •
IgE antibodies against the mammalian oligosaccharide allergen galactose-α-1,3-galactose (αGal) can result in a severe allergic disease known as alpha-gal syndrome (AGS). This syndrome, acquired by tick bites that cause αGal sensitization, leads to allergic reactions after ingestion of non-primate mammalian meat and mammalian-derived products that contain αGal. Allergen-specific immunotherapies for this tickborne allergic syndrome are understudied, as are the immune mechanisms of allergic desensitization that induce clinical tolerance to αGal. Here, we reveal that prophylactic administration of αGal glycoprotein-containing nanoparticles to mice prior to tick protein-induced αGal IgE sensitization blunts the production of Th2 cytokines IL-4, IL-5, and IL-13 in an αGal-dependent manner. Furthermore, these effects correlated with suppressed production of αGal-specific IgE and hypersensitivity reactions, as measured by reduced basophil activation and histamine release and the systemic release of mast cell protease-1 (MCPT-1). Therapeutic administration of two doses of αGal-containing nanoparticles to mice sensitized to αGal had partial efficacy by reducing the Th2 cytokine production, αGal-specific IgE production, and MCPT-1 release without reducing basophil activation or histamine release. These data identify nanoparticles carrying encapsulated αGal glycoprotein as a potential strategy for augmenting αGal-specific immune tolerance and reveal diverse mechanisms by which αGal nanoparticles modify immune responses for established αGal-specific IgE-mediated allergic reactions.