Bovine γ-globulin, lactoferrin, and lactoperoxidase are relevant bovine milk allergens in patients with α-Gal syndrome

Background Mammalian meat is the most common trigger of the allergic reactions in patients with alpha-Gal syndrome (AGS). Milk and dairy, although less often, also cause a significant number of allergic manifestations. The aim of this study was to identify alpha-Gal-containing bovine milk proteins with allergenic properties among AGS patients. Methods Thirty-eight AGS patients with IgE to milk were included in the study. Milk proteins were analyzed for the presence of alpha-Gal and for binding by patients' IgE using immunoblot, ImmunoCAP, and inhibition ELISA. Allergenicity of milk and milk proteins was assessed by basophil activation test. Results More than half of the AGS patients reported allergic reactions to milk or dairy products. Bovine gamma-globulin (BGG), lactoferrin (LF), and lactoperoxidase (LPO) were identified as alpha-Gal carrying proteins which were recognized by AGS patients' IgE. Whey mirrored the anti-alpha-Gal and IgE reactivity of BGG, LF, and LPO. Eighty-nine percent of the patients displayed IgE to BGG, 91% to LF, and 57% to LPO. Inhibition of alpha-Gal-specific IgE binding was achieved by BGG, LF, LPO, and whey. These proteins also activated AGS patients' basophils. Interestingly, at lower concentrations, LF was the most potent inhibitor of IgE binding, and the most potent activator of basophils. Conclusion BGG, LF, and LPO were all found to be relevant milk alpha-Gal-containing glycoproteins that bound AGS patients' IgE antibodies and activated their basophils. These proteins are probably involved in the allergic reactions to milk in AGS patients. LPO was for the first time shown to be an allergen.