IgG to Galactose-Alpha-1,3-Galactose: Impact of Alpha-Gal IgE Sensitization, Blood Type, and Tick Bites

Abstract

Background: Antibodies to galactose-alpha-1,3-galactose (alpha-gal), particularly the IgM and IgG isotypes, are abundant in human sera. These antibodies are known to be an important xenotransplantation barrier, but the full implications of these antibodies to health and disease remain incompletely understood. By contrast, IgE to alpha-gal is uncommon in the population but has been associated with tick bites and causally linked with mammalian meat allergy, often now known as alpha-gal syndrome (AGS). To date, there have been few population-based studies that have investigated alpha-gal IgG levels in relation to demographic factors, diet, tick bites, and mammalian meat allergy. Methods: Adults, predominantly healthcare workers, were recruited for a COVID-19 vaccine study. At least one serum sample was collected, and subjects completed questionnaires to provide demographic, diet, and tick exposure data. Alpha-gal IgG, IgE, and total IgG were measured using the ImmunoCAP platform, and blood group was assessed via reverse typing using stored serum. We also assessed alpha-gal IgG levels among subjects with AGS, recruited from an allergy clinic. Results: The median age of the 267 subjects in the vaccine cohort was 42 years, and median alpha-gal IgG levels were 3.0 μg/mL. Alpha-gal IgG levels were higher among the 43 (16.1%) subjects who had alpha-gal IgE sensitization (≥0.1 IU/mL) and among subjects lacking the B blood group antigen (blood groups A and O). Alpha-gal IgG levels did not differ between the subjects who had asymptomatic alpha-gal IgE sensitization and those who had meat allergy. However, both groups had higher alpha-gal IgG levels than subjects who lacked alpha-gal IgE sensitization. Subjects who reported prior tick or chigger bites had higher alpha-gal IgG levels than those without a bite history, regardless of alpha-gal IgE sensitization status. Conclusions: In a population-based cohort, alpha-gal IgG antibodies were found to be prevalent, and levels were increased in subjects with blood groups A and O, subjects who were alpha-gal IgE sensitized, and those who reported a history of tick bites.

Keywords: IgE; IgG; alpha-gal; red meat allergy; ticks.

Figure 1

Comparison of alpha-gal IgG assay results (μg/mL) using alpha-gal HSA on the solid phase and results from the commercially available Thermo-Fisher bovine thyroglobulin alpha-gal assay (o215). (A) Alpha-gal IgG levels measured among 81 samples from the COVID-19 vaccine cohort. (B) Alpha-gal IgG levels measured among samples from 38 AGS patients.

Figure 2

Alpha-gal IgG levels (μg/mL) among subjects in the COVID-19 vaccine cohort. (A) Alpha-gal IgG levels stratified by age. (B) Alpha-gal IgG levels stratified by sex. (C) Alpha-gal IgG stratified by race. (D) Alpha-gal IgG levels stratified by blood group among those expressing the B antigen (AB/B) and those not expressing the B antigen (A/O). (E) Alpha-gal IgG levels stratified by alpha-gal IgE sensitization status. (F) Alpha-gal IgG levels stratified by mammalian meat consumption (“+” = 1–2 servings/week; “++” = ≥3 servings/week), with blue squares indicating those also avoiding dairy (n = 263 with complete dietary data set).

Figure 3

Alpha-gal IgG levels, (A) stratified by blood group status and alpha-gal IgE sensitization status, and (B) in relation to alpha-gal IgE levels (bottom left: n = 16 with undetectable alpha-gal IgG and alpha-gal IgE).

Figure 4

Alpha-gal IgG levels in relation to alpha-gal IgE sensitization and symptomatic mammalian meat allergy among the COVID-19 vaccine cohort and the AGS patient cohort.

Figure 5

Receiver operating characteristic (ROC) analysis predicting symptomatic AGS among subjects with positive alpha-gal IgE results (IgE ≥ 0.1 IU/mL). (A) Optimal alpha-gal IgE cutoff and (B) ROC curves comparing the diagnostic value of alpha-gal IgE and IgG in predicting AGS.

Figure 6

Alpha-gal IgE prevalence and IgG levels in relation to tick/chigger exposure. (A) The prevalence of alpha-gal IgE among 207 subjects in the vaccine cohort, based on their answer to questions regarding tick/chigger bite history. (B) The levels of alpha-gal IgG among 207 subjects in the vaccine cohort, based on their answer to questions regarding tick/chigger bite history. (C) Alpha-gal IgG levels among 166 subjects from the vaccine cohort who were not sensitized to alpha-gal (alpha-gal IgE < 0.1 IU/mL), stratified by tick/chigger bite history.