Microarray Patch Based Transdermal Allergen Immunotherapy Prevents Gliadin-induced Anaphylaxis in a Murine Model

Abstract

Purpose: Gliadins are the primary triggers in wheat-dependent exercise-induced anaphylaxis. Currently, there are no officially approved immune-modulating treatments for gliadin allergy. Recent in vivo studies have shown that hyaluronic acid based dissolving microarray patch (dMAP) could deliver house dust mite allergens through transdermal pathway and protect allergic asthma and atopic dermatitis in vivo. In this study, we explored the potential of dMAP for the transdermal delivery of gliadin proteins as a strategy to mitigate gliadin allergy.

Methods: C3H/HeJ mice were sensitized to gliadin with cholera toxin via oral administration, followed by oral or intraperitoneal gliadin challenge. To evaluate the protective effects of transdermal immunotherapy (TDIT), gliadin-loaded dMAPs were applied twice a week to gliadin-sensitized mice for 4 weeks. Afterward, the mice were challenged with gliadin.

Results: The manufacturing process of dMAP did not alter the allergenicity of gliadin. TDIT significantly improved the anaphylaxis clinical score and stabilized core body temperature in the gliadin anaphylaxis model. It reduced mast cell protease-1 and gliadin-specific immunoglobulin E (IgE), and increased specific IgG₁, IgG2a and IgG2b levels. Ex vivo splenocyte study revealed that TDIT enhanced T helper type 1 (Th₁) cell population, interferon-γ expression, regulatory T cell population, and interleukin (IL)-10 expression, as well as suppressed Th₂ cell population and associated cytokines (IL-4, IL-5, and IL-13). Furthermore, this TDIT preserved the structural integrity of small intestinal villi and reduced eosinophil and mast cell infiltration.

Conclusions: Gliadin TDIT using dMAP mitigates gliadin-induced anaphylaxis in a murine model, offering a promising novel immune modulating treatment for gliadin-induced anaphylaxis.