Alpha-gal syndrome is an unconventional food allergy, characterized by IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal) and not to a food-protein. In this review, we discuss how alpha-gal syndrome reframes our current conception of the mechanisms of pathogenesis of food allergy. The development of alpha-gal IgE is associated with tick bites though the possibility of other parasites promoting sensitization to alpha-gal remains. We review the immune cell populations involved in the sensitization and effector phases of alpha-gal syndrome and describe the current understanding of why allergic responses to ingested alpha-gal can be delayed by several hours. We review the foundation of management in alpha-gal syndrome, namely avoidance, but also discuss the use of antihistamines, mast cell stabilizers, and the emerging role of complementary and alternative therapies, biological products, and oral immunotherapy in the management of this condition. Alpha-gal syndrome influences the safety and tolerability of medications and medical devices containing or derived from mammalian products and impacts quality of life well beyond food choices.
In the last decade, there has been increasing research dedicated to food immunotherapy to induce clinical desensitization and provide protection by increasing clinical reaction thresholds. Results from recent food immunotherapy studies with differing routes of administration (oral, sublingual, and epicutaneous) suggest that food immunotherapy can induce clinical desensitization with varying levels of safety, however lasting tolerance has not been demonstrated. Furthermore, treatment side effects and dosing logistics may make the therapies difficult for some supporting the need for alternative treatment approaches. Peptide immunotherapy and DNA vaccine approaches should in theory allow for safer administration by decreasing allergenicity but proof of their clinical efficacy and immunogenicity remains to be proven. Biologic agents may allow for increased safety and rapid up-dosing of immunotherapy with the added benefit of treating multiple allergens simultaneously.
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