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

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.

A WAO — ARIA — GA2LEN consensus document on molecular-based allergy diagnosis (PAMD@): Update 2020

“…227 Tick feeding induces the production of alpha-gal-containing proteins in tick salivary glands, even after feeding on human blood not containing alpha-gal, implying that the alpha-gal-containing proteins are inherent tick proteins, not transferred via a prior blood meal. 228 Feeding causes increased tick galactosyltransferase expression in the midgut and increased alpha-gal levels throughout the tick. 229 Alpha-gal is also present also on cat IgA Fel d 5 and IgM Fel d 6; however, crosssensitization between cat antigens and alpha-gal is not clinically relevant.…”

Stemming the Rising Tide of Human-Biting Ticks and Tickborne Diseases, United States

“…For public health messaging, surveillance of ticks and their associated pathogens is especially useful at the leading edges of an expanding vector tick species range. Moreover, the negative effect of ticks on human health is expanding from long-recognized pathogen transmission and tick paralysis to also include an allergic response to red meat believed to be associated with previous bites by ticks, including the lone star tick (Amblyomma americanum) (30). Our most recent warning signal was the introduction and establishment along the Eastern Seaboard of an invasive tick species (the Asian longhorned tick, Haemaphysalis longicornis) with potential to negatively impact the cattle industry and perhaps also public health if this tick is found to commonly bite humans in the United States (31).…”

A Common Food Glycan, Pectin, Shares an Antigen with Streptococcus pneumoniae Capsule

“…A 1% concentration of human IgG targets the antigen (17); thus, the antibody may be protective against the normal intestinal flora expressing LPS with the antigen (18). IgE antibodies are also created in some individuals following tick bites and cause an allergy to red meat (19,20). Another example of a food antigen that interferes with immune responses in humans is the N-glycolylneuraminic acid present in red meat.…”