AUTHOR=Crispell Gary , Commins Scott P. , Archer-Hartman Stephanie A. , Choudhary Shailesh , Dharmarajan Guha , Azadi Parastoo , Karim Shahid 

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

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01056

DOI=10.3389/fimmu.2019.01056

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>Amblyomma americanum</italic>), the Gulf-Coast tick (<italic>Amblyomma maculatum</italic>), the American dog tick (<italic>Dermacentor variabilis</italic>), and the black-legged tick (<italic>Ixodes scapularis</italic>) by using a combination of immunoproteomic approach and, carbohydrate analysis. Anti-α-gal antibodies identified α-gal in the salivary glands of both <italic>Am. americanum</italic> and <italic>Ix. scapularis</italic>, while <italic>Am. maculatum</italic> and <italic>De. variabilis</italic> 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. <italic>Am. americanum</italic> 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 <italic>Am. americanum</italic> and <italic>Ix. scapularis</italic> have α-gal in their saliva and salivary glands, but <italic>Am. maculatum</italic> contains no detectable quantity. Consistent with the glycan analysis, salivary samples from <italic>Am. americanum</italic> and <italic>Ix. scapularis</italic> 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.</p>