Tick molecular factors associated with alpha-gal syndrome (AGS)

Alpha-gal syndrome (AGS, also known as red meat allergy (RMA), is caused by the increased production of IgE antibodies against galactose-alpha-1,3-galactose (alpha-gal or aGal). This glycan is found in most mammals, except Old World monkeys and humans. AGS is observed in susceptible individuals after ingesting red meat, with a clinical manifestation of urticaria and anaphylaxis. Previous reports indicate that bites of the lone star tick (Amblyomma americanum) are the leading cause of the initial sensitization to AGS in humans. However, this condition has been associated with tick bites from different species worldwide, including Ixodes spp. in Europe and Australia, Amblyomma spp. in North America, and Hemaphysalis longicornis in Asia.

While bites of the lone star tick containing aGal are the main AGS sensitizers, the source of aGal in tick salivary secretions remains unknown. In our previous work, we reported that ticks fed on alpha-gal-containing blood sources contained lower levels of alpha-gal than those ticks fed on human blood (an alpha-gal-free blood source). This, combined with the knowledge that the aGal levels of the unfed tick are negligible and that the alpha-galactosyltransferase (a1,3GT) orthologue gene has not been detected in ticks, suggests that ticks can produce aGal during feeding on human blood via an unknown mechanism.

Furthermore, suspected cases of AGS in the West Coast and Southwest regions of the United States have been reported. Thus, our lab aims to investigate the potential for different tick species commonly found in the West and Southwest of the United States to transmit AGS to humans. These include the western black-legged tick (Ixodes pacificus), the brown dog tick (Rhipicephalus sanguineus), and the rocky mountain wood tick (Dermacentor andersoni).

This work aims to identify the sources of aGal in ticks and the molecular factors associated with aGal production while assessing the potential for North American ticks to transmit AGS. Our findings can aid in the future development of an anti-tick vaccine or anti-aGal-tick vaccine, which could help reduce the incidence of tick-borne illnesses.