Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis

Abstract

Wheat is a prominent allergenic food that can trigger life-threatening anaphylaxis. Presently, it remains unclear whether wheat glutenin (WG) extract possesses inherent sensitization potential independently, without the use of adjuvants, and whether it can sensitize mice to the extent of inducing life-threatening systemic anaphylaxis. In this study, we tested the hypothesis that repeated skin exposures to WG extract without adjuvant will sensitize mice with the resultant anaphylactic reaction upon systemic WG challenge. Balb/c mice were bred and maintained on a strict plant protein-free diet and were repeatedly exposed to a WG extract or vehicle once a week for 9 weeks. WG-specific (s)IgE and total (t)IgE levels were quantified. Mice were challenged with WG extract to induce anaphylactic reactions as measured by hypothermic shock response (HSR) and mucosal mast cell degranulation response (MMCR). We also conducted proteomic analysis of 120 spleen immune markers. These skin-sensitized mice exhibited exposure-dependent IgE responses and near-fatal anaphylaxis upon challenge. Proteomic analysis identified seven dramatically elevated immune biomarkers in anaphylactic mice. These data reveal that WG is intrinsically allergenic, and that chronic skin exposure to WG extract can prime the mice for potentially fatal anaphylaxis.

Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development

“…Recent research shows that mechanisms underlying adjuvant-based versus adjuvant-free models of food allergy can be substantially different [80]; since human gluten allergenicity is pathogenesis typically does not involve adjuvants such as alum, adjuvant-free models might be more helpful in developing therapeutics for human application. Adjuvant-free models of gluten hypersensitivity reported recently can be employed for this purpose [60,61]; furthermore, most animal models have focused on systemic anaphylaxis only; animal models of other types of hypersensitivities caused by gluten (atopic dermatitis, baker's asthma, etc.) are urgently needed for preclinical testing of novel diet-based therapeutics in development (Figure 1).…”

“…Additionally, the immune reactivity study focused solely on ω-5 gliadin, necessitating future exploration of the tannin treatment effects on other wheat allergens to comprehensively understand its potential impact. Furthermore, future in vivo testing using preclinical animal models will be necessary as a crucial step preceding eventual human clinical trials [60,61].…”

“…Further in vivo testing in preclinical animal models would allow for the evaluation of CRISPR-Cas9 editing's effect on potentially reduced clinical allergic reactivity. This step is essential before progressing to clinical trials involving human subjects [60,61].…”