Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies.
Methods:The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 + basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed | 1801 DUAN et Al.
Background
Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE‐crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen‐specific, IgE‐mediated smooth muscle contractions using precision cut intestinal slices (PCIS).
Methods
PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0 to 24 h. Distribution of relevant cell subsets was confirmed using single nucleus RNA sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut‐sensitized non‐allergic donors, and exposed to various stimuli including serotonin, histamine, FcɛRI‐crosslinker, and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed.
Results
PCIS viability was maintained for 24 h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen‐specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE‐dependent mast cell‐derived mediator release. Antihistamines suppressed histamine‐induced contraction and plasma from successful peanut OIT suppressed peanut‐specific PCIS contraction.
Conclusion
PCIS represent a novel human tissue‐based model to study acute, IgE‐mediated food allergy and pharmaceutical impacts on allergic responses in the gut.
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