? 2022Background: The disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal–specific IgE (sIgE) antibodies. Objective: To evaluate tick exposure as a risk factor for AGS and elevated alpha-gal sIgE level. Methods: We conducted a case-control study comparing patients with AGS from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tick-borne pathogens. Results: The patients with AGS were more likely to recall finding a tick on themselves (odds ratio OR, 11.20; 95 confidence interval CI, 4.97-25.15), live near wooded forest (OR, 2.27; 95 CI, 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR, 5.58; 95 CI, 2.56-12.19). The patients with AGS were also more likely to report 4 or more tick bites (OR, 33.05; 95 CI, 9.92-155.12) and reactions at the site of tick bites (OR, 7.93; 95 CI, 3.74-16.80). Furthermore, elevated alpha-gal sIgE level was observed in 33 of the controls and was associated with tick exposure in the controls (OR, 4.25; 95 CI, 2.21-8.18). Conclusion: The results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE level.
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