Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy

• Published in: Frontiers in immunology Vol. 10; p. 1056
• Main Authors: Crispell, Gary, Commins, Scott P., Archer-Hartman, Stephanie A., Choudhary, Shailesh, Dharmarajan, Guha, Azadi, Parastoo, Karim, Shahid
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.05.2019
• Subjects: glycans; Immunology; red meat allergy; saliva; salivary glands; ticks; α-gal; saliva; glycans; ticks; red meat allergy; Amblyomma americanum; salivary glands; α-gal; Ixodes scapularis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.01056

Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick ( ), the Gulf-Coast tick ( ), the American dog tick ( ), and the black-legged tick ( ) by using a combination of immunoproteomic approach and, carbohydrate analysis. Anti-α-gal antibodies identified α-gal in the salivary glands of both and , while and appeared to lack the carbohydrate. PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands. Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks. ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal. N-linked glycan analysis revealed that and have α-gal in their saliva and salivary glands, but contains no detectable quantity. Consistent with the glycan analysis, salivary samples from and stimulated activation of basophils primed with plasma from α-gal allergic subjects. Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.