An Adjuvant-Free Mouse Model Using Skin Sensitization Without Tape-Stripping Followed by Oral Elicitation of Anaphylaxis: A Novel Pre-Clinical Tool for Testing Intrinsic Wheat Allergenicity (1)

The prevalence of wheat allergy in the United States among adults is 0.9%−3.6%. Its prevalence among United States children is 0.2%−1.3%. An adjuvant-free mouse model to study oral elicitation of anaphylaxis to wheat is unavailable at present–the focus of this study. Among the mouse strains, Balb/c was shown to exhibit wheat allergenicity similar to that of humans.

A robust induction of sIgE antibody levels after transdermal exposure with SSPE but no vehicle was noted. A dramatic increase in tIgE levels was observed in SSPE-sensitized but not in vehicle-sensitized mice.

Acute HSRs were observed upon oral allergen challenge in skin-sensitized mice. Significant HSRs were noted from 15 to 30mins.

Both sIgE and tIgE showed significant correlations with temperature differences; however, the sIgE levels consistently showed stronger correlations with temperature differences than did the tIgE levels.

Allergic mice exhibited robust MMCP-1 responses upon oral allergen challenge with 20 mg dose.

There was a strong correlation (r = −0.88) between MMCR and HSR from 15 to 30min post-challenge period.

Only sIgE showed a strong correlation with MMCR.

Durum wheat SSPE-sensitized mice had significantly higher levels of prototypic Th2 cytokines (IL-4, IL-5) and a Th17 (IL-17E) cytokine. Also, Th1 cytokines (IFN-γ and IL-12p70) were elevated.

Four chemokines were also significantly elevated upon oral allergen but not the saline challenge of skin-sensitized mice, such as CCL5, CCL20, CCL22, and CXCL1.

IL-4 and IL-5 in the lung fluid of gliadin elevated in allergic mice challenged by nasal route. Besides these prototypic Th2 cytokines, elevation of Th1 and Th17 cytokines in mice had developed atopic dermatitis upon chronic intraperitoneal exposures to durum wheat SSPE with alum-adjuvant. Th1, Th2, and Th17 cytokines were increased in both an alum-adjuvant mouse model, as well as in an adjuvant- free mouse model upon intraperitoneal injections with durum wheat SSPE.

1. H. Gao, R. Jorgensen, R. Raghunath, P. K. W. Ng, V. Gangur, An Adjuvant-Free Mouse Model Using Skin Sensitization Without Tape-Stripping Followed by Oral Elicitation of Anaphylaxis: A Novel Pre-Clinical Tool for Testing Intrinsic Wheat Allergenicity. Frontiers in Allergy. 3 (2022), doi:10.3389/falgy.2022.926576.