Red Meat Allergy May Develop Independent of Tick Blood Meal Status

Alpha-gal syndrome (AGS) is a paradigm-shifting food allergy characterized by delayed reactions to non-primate mammalian meat and derived products. Evidence continues to suggest that AGS develops following tick bites and multiple species have been implicated globally. Tick saliva may contain alpha-gal from prior blood meal or may act as an adjuvant to induce IgE. This study assessed whether tick salivary gland extract (TSGE) could activate alpha-gal-sensitized basophils directly and if IgE reactivity was present in tick saliva. PBMCs containing basophils from a non-alpha-gal allergic control subject were stripped of IgE; primed with plasma from subjects with and without alpha-gal allergy; stimulated for 30 minutes with TSGE from 4 species of ticks; and assessed for basophil activation by FACS. IgE reactivity was assessed by immunoassay using TSGE, tick larvae extract and tick saliva. The frequency of CD63+ basophils was 40-fold higher when alpha-gal IgE-sensitized basophils were stimulated with TSGE from Lone Star ticks compared to baseline. Extract from Ixodes scapularis but not the Gulf Coast tick, Amblyomma maculatum, also increased basophil activation. IgE reactivity was found in tick saliva (mean 23.4 IU/mL±1.9) among subjects with AGS but not larval tick or partially fed TSGE. IgE from subjects with AGS recognizes an antigen present in ticks from some species but not all and this observation can lead to identification of the sensitizing allergen. Interestingly, IgE reactivity appears to be specifically retained in tick saliva, an important distinction that may suggest alpha-gal antigen is present in ticks independent of blood meal status.