Pathogenic effector TH2 cells discriminate between allergic and eosinophilic inflammation in food allergy and eosinophilic gastrointestinal disease

Abstract

Abstract IgE-mediated food allergies (FA) and delayed food-triggered (FT) gastrointestinal tissue eosinophilia (EGID) have distinct clinical manifestations and are treated differently. Pathogenic effector TH2 (peTH2) cells are implicated in inappropriate TH2 responses in both of these diseases. Furthermore, EGID patients can have concomitant FA, and some EGID patients do not report any food triggers. To better understand the role of peTH2 cells in the context of FA and EGID and the overlap between these two conditions, peTH2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) from purified peripheral blood mononuclear cells (PBMC) were profiled by intracellular cytokine flow cytometry in these deeply-characterized patient cohorts: patients with FA alone (FA, n=5), EGID with FA and FT (EGID+FA+FT, n=7), EGID with FT (EGID+FT, n=7) and EGID without FA or FT (EGID, n=9). Patients with any food allergy or food trigger (FA, EGID+FA+FT, and EGID+FT) have increased peTH2 cells compared to healthy volunteers (HV). Interestingly, a greater percentage of peTH2 cells in patients with food triggers (EGID+FA+FT, EGID+FT) exhibit a trend toward IL5+IL13+ double positivity (P = 0.0556) than those from patients without food triggers (FA, EGID). In contrast, peTH2 cells from patients with FA had a greater percentage that were IL17A+ (P=0.009) or IFNγ+ (P=0.0444) than patients with eosinophilic disease (EGID+FA+FT, EGID+FT, EGID). Our studies indicate that while elevated levels of peTH2 cells are indicative of allergic inflammation of both immediate hypersensitivity and eosinophilic disease, the cytokine profile of each disorder may be distinct, where IL17A+ and IFNγ+ predominate in those without eosinophilic disease.