Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome

• Published in: Journal of allergy and clinical immunology Vol. 149; no. 2; pp. 698 - 707.e3
• Main Authors: Murangi, Tatenda, Prakash, Prema, Moreira, Bernardo Pereira, Basera, Wisdom, Botha, Maresa, Cunningham, Stephen, Facey-Thomas, Heidi, Halajian, Ali, Joshi, Lokesh, Ramjith, Jordache, Falcone, Franco H., Horsnell, William, Levin, Michael E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2022
• Subjects: Alpha-gal; Amblyomma hebraeum; anaphylaxis; Animals; Antigens, Helminth - immunology; Ascaris lumbricoides; Ascaris lumbricoides - immunology; Cells, Cultured; Disaccharides - analysis; food allergy; Food Hypersensitivity - etiology; galactose-alpha-1,3-galactose; helminths; Humans; Immunoglobulin E - immunology; meat allergy; Rats; red meat allergy; Rhipicephalus evertsi; ticks; Ticks - immunology; Ascaris lumbricoides; galactose-alpha-1,3-galactose; ticks; HRP; meat allergy; E/S; anaphylaxis; Rhipicephalus evertsi; food allergy; Strep-HRP; PBS-T; Asc l; BTG; scFv; red meat allergy; Amblyomma hebraeum; GSI-B4; helminths; Alpha-gal
• DOI: 10.1016/j.jaci.2021.07.018
• ISSN: 0091-6749; 1097-6825

IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (delayed anaphylaxis after ingestion of mammalian meat). Development of sensitization has been attributed to tick bites; however, the possible role of other parasites has not been well studied. Our aims were to assess the presence, relative abundances, and site of localization of alpha-gal–containing proteins in common ectoparasites and endoparasites endemic in an area of high prevalence of alpha-gal syndrome, as well as to investigate the ability of ascaris antigens to elicit a reaction in a humanized rat basophil in vitro sensitization model. Levels of total IgE, Ascaris-specific IgE, and alpha-gal IgE were measured in sera from patients with challenge-proven alpha-gal syndrome and from controls without allergy. The presence, concentration, and localization of alpha-gal in parasites were assessed by ELISA, Western blotting, and immunohistochemistry. The ability of Ascaris lumbricoides antigen to elicit IgE-dependent reactivity was demonstrated by using the RS-ATL8 basophil reporter system. Alpha-gal IgE level correlated with A lumbricoides–specific IgE level. Alpha-gal protein at 70 to 130 kDa was detected in A lumbricoides at concentrations higher than those found in Rhipicephalus evertsi and Amblyomma hebraeum ticks. Immunohistochemistry was used to localize alpha-gal in tick salivary acini and the helminth gut. Non–alpha-gal–containing A lumbricoides antigens activated RS-ATL8 basophils primed with serum from subjects with alpha-gal syndrome. We demonstrated the presence, relative abundances, and site of localization of alpha-gal–containing proteins in parasites. The activation of RS-ATL8 IgE reporter cells primed with serum from subjects with alpha-gal syndrome on exposure to non–alpha-gal–containing A lumbricoides proteins indicates a possible role of exposure to A lumbricoides in alpha-gal sensitization and clinical reactivity.