IgE to the Mammalian Oligosaccharide Galactose-α-1,3-Galactose Is Associated With Increased Atheroma Volume and Plaques With Unstable Characteristics-Brief Report

Abstract

Objective: Emerging evidence suggests a link between coronary artery disease and type 2 immunity. We sought to test the hypothesis that IgE sensitization to the mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal)-the target allergen of delayed anaphylaxis to red meat-is associated with coronary artery disease.

Approach and results: Total IgE and specific IgE to α-Gal were assayed on sera from 118 subjects who presented for cardiac catheterization and underwent intravascular ultrasound. IgE to α-Gal was detected in 26%, and atheroma burden was higher in sensitized subjects (P=0.02). Because α-Gal sensitization relates to an environmental exposure that could be a risk factor for early-onset coronary artery disease (ie, tick bites), we age stratified the cohort. In subjects ≤65 years of age, the strength of the association with atheroma burden was stronger (P<0.001), and plaques in the sensitized group had less stable features based on intravascular ultrasound. To address the specificity of the association with IgE to α-Gal, IgE to inhalants and peanut were assayed and were not associated with coronary artery disease. Total IgE and α-Gal-specific IgE were strongly associated with each other, but the strength of the relationship with atheroma burden was stronger for α-Gal-specific IgE. This association was significant when adjusted for sex, diabetes mellitus, hypertension, statin use, and total IgE (regression coefficient, 12.2; SE, 5.2; P=0.02).

Conclusions: Increased atheroma burden and plaques with more unstable features were associated with IgE to α-Gal-an effect most pronounced in subjects ≤65 years of age. IgE sensitization to α-Gal may represent a novel, and potentially modifiable, risk factor for coronary atherosclerosis.

Keywords: atherosclerosis; galactosyl-(1-3)galactose; immunoglobulin E; red meat; risk factors.

Figure.

A, Representative examples of intravascular ultrasound (IVUS) with fibrous (dark green), fibrofatty (light green), necrotic (red), and calcified plaques (white) evident. B, Results of IVUS in total cohort and when stratified by age. C, Results of IVUS virtual histology in subjects ≤65 y of age. Data in B and C show mean with 95% confidence interval (CI) where each data point represents 1 subject and comparison is with the Mann–Whitney U test. Percentage differences in the mean value between galactose-α-1,3-galactose (α-Gal)–positive and α-Gal–negative subjects within an age group are represented in B by Δ. sIgE indicates specific IgE.