Volume 124, Issue 6 , Pages 1326-1332.e6, December 2009
Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5− TH2 responses
Background
Both anaphylactic food allergy and eosinophil-associated gastrointestinal disorders are associated with TH2 responses and food-specific IgE, yet they have very different clinical presentations.
Objective
To determine whether the clinical differences between anaphylactic food allergy and eosinophil-associated gastrointestinal disorders are reflected in different TH2 responses to foods.
Methods
Subjects with peanut allergy (PA), subjects with allergic eosinophilic gastroenteritis (AEG), and nonatopic subjects were enrolled. Antigen-specific IL-4, IL-5, IFN-γ, and TNF T-cell responses to peanut, soy, and shrimp were measured by using intracellular cytokine staining and polychromatic flow cytometry.
Results
Two distinct subpopulations of TH2 cells were found: IL-5+ TH2 (IL-4+, IL-5+) and IL-5– TH2 (IL-4+, IL-5–) cells. Peanut-specific IL-5+ TH2 cells were present at a 20-fold greater frequency in AEG versus PA (81 vs 4 per 106 CD4 cells; P = .05), whereas there were similar frequencies of IL-5- TH2 cells (67 vs 41 per 106). For all foods, IL-5+ TH2 cells accounted for a significantly greater fraction of the antigen-specific cells in AEG relative to PA (29% vs 4%; P < .0001). In PA but not AEG, IL-5– TH2 responses to peanut were highly correlated with peanut-specific IgE (r = 0.87 vs 0.55, respectively). All subject groups elicited similar very low-magnitude TH1 responses to food antigens.
Conclusion
TH2 responses are composed of 2 subpopulations: IL-5+ TH2 and IL-5– TH2 cells. IL-5+ TH2 food allergen–specific T cells are singularly associated with AEG, whereas PA is associated with a dominant IL-5– TH2 response. These results suggest heterogeneity within the TH2 cytokine response, with different TH2 responses alternatively favoring IgE-mediated or eosinophil-dominant immunopathology.
Key words: Food allergy, peanut, T cell, TH2, eosinophil-associated gastrointestinal disease, IL-4, IL-5, flow cytometry
Abbreviations used: AEG, Allergic eosinophilic gastroenteritis, EG, Eosinophilic gastroenteritis, EGID, Eosinophil-associated gastrointestinal disorder, EoE, Eosinophilic esophagitis, NA-EG, Nonallergic eosinophilic gastroenteritis, NIAID, National Institute of Allergy and Infectious Diseases, PA, Peanut allergy
Supported by the National Institute of Allergy and Infectious Diseases, NIH, Intramural Research Program.
Protocol clinicaltrials.gov identifiers: NCT00084097, NCT00001756, NCT00557895.
Disclosure of potential conflict of interest: C. Prussin owned stock in Affymetrix and receives research support from NIAID/NIH. The rest of the authors have declared that they have no conflict of interest.
PII: S0091-6749(09)01468-7
doi:10.1016/j.jaci.2009.09.048
© 2009 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Volume 124, Issue 6 , Pages 1326-1332.e6, December 2009
