A distinct T helper subset contributes to the pathogenesis of classical Th2-mediated food allergy disorders
Monday, March 5, 2018: 3:00 PM
S330GH (Convention Center)
Nahir Garabatos, PhD, , ,
RATIONALE: Peanut food allergy is heterogeneous. Identification of specific subpopulations of peanut-reactive T cells involved in disease development may further our understanding of pathophysiology and treatment response tailoring patient management.

METHODS: Peanut allergic subjects (PA, n=20) aged 13 to 65 years were recruited basis on their clinical history, serum IgE (> 0.35 kU/L) and positive skin prick test to peanut, and positive reaction to peanut during oral food challenge. Non allergic subjects (n=10) were used as a control group. Peanut-reactive CD4+ T cells were tracked and profiled ex vivo using CD154 upregulation assay. Single-cell RNA sequencing, surface markers and cytokine profile analysis were performed to examine this cell response.

RESULTS: Our data emphasize the heterogeneity of peanut-reactive effector T cell responses, with two mutually exclusive phenotypic entities (CCR6-CRTH2+ and CCR6+CRTH2-) associated with food allergy. Serum IgE levels to peanut vary across PA, but show positive correlation with CRTH2 expression. Single-cell analysis reveals heterogeneity of peanut-reactive T cells in PA where two different gene clusters were detected. While CRTH2+CCR6- peanut-specific T cell subset shared similar features with Th2A cell responses (i.e. IL33R+, IL25R+, IL-5), CCR6+CRTH2- T cell subset exhibit a Th17/Th1-related activity, suggesting a distinct pathway that may form the basis of a clinically relevant food allergy endotype.

CONCLUSIONS: Our data suggest that peanut allergic subjects can be classified into 2 endotypes, the Th2A-high and the Th2A-low endotype. Food allergy may no longer be considered as a single entity with “one size fits all” approaches to diagnosis and treatment.