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

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

doi:10.3389/fimmu.2019.01056

Abstract

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

Highlights

Food allergies are a growing food safety and public health concern, and according to the Centers for Disease Control and Prevention, food allergies are estimated to affect 4–6% of children, and 4% of adults in the United States [1]
The species chosen for this study were Ix. scapularis, Am. maculatum, Am. americanum, and De. variabilis because they are the most prevalent tick species found in the Southeastern region of the United states, where initially there were a majority of the alpha-gal syndrome (AGS)-reported cases
The results indicated that the anti-α-gal antibody had cross-reactivity to partially-fed Am. americanum salivary glands and saliva (Figure 1)

Summary

Introduction

Food allergies are a growing food safety and public health concern, and according to the Centers for Disease Control and Prevention, food allergies are estimated to affect 4–6% of children, and 4% of adults in the United States [1]. Delayed hypersensitivity reactions to foods (e.g., eczema) are not uncommon, and generally develop several hours after allergen exposure [3]. While food allergies generally are associated with immune responses to specific proteins, a novel IgE antibody response to the oligosaccharide epitope galactose-alpha-1,3galactose (alpha-gal or α-gal) found in mammalian food products (e.g., beef and pork) has been reported [4]. This delayed hypersensitivity, termed red meat allergy or alpha-gal syndrome (AGS), appears to develop at any age, often with several decades of clear immunologic tolerance to mammalian meat

Methods

Results

Conclusion