Elucidation of Desensitization Mechanisms Induced by Oral Immunotherapy in a Rat Model of Ovalbumin Allergy

TL;DR

This study explores how oral immunotherapy reduces allergic reactions in rats by inhibiting IgE binding through increased IgG.

Contribution

The study identifies a novel mechanism by which OIT suppresses allergic responses via IgG-mediated inhibition of IgE crosslinking.

Findings

OIT suppressed rectal temperature decrease and histamine increase in OVA-sensitized rats.

OIT increased OVA-specific IgG1 levels but not IgE levels compared to non-OIT groups.

IgG from OIT rats inhibited sIgE-OVA crosslinking, as shown by AlphaCL assays after IgG removal.

Abstract

Oral immunotherapy (OIT) is a promising approach for treating food allergy. Here, we elucidated the mechanisms of desensitization induced by OIT in rats sensitized to ovalbumin (OVA). The desensitization was induced by ingestion of OVA three times per week after sensitization in rats. OIT suppressed the decrease in rectal temperature and increase in plasma histamine levels induced by OVA injection immediately and 4 weeks after OIT completion. Plasma OVA-specific IgE (sIgE) levels did not differ between the non-OIT and OIT groups, but OVA-specific IgG1 levels were higher in the OIT group than in the non-OIT group at both timepoints. To evaluate IgG’s effect on IgE crosslinking with OVA, amplified luminescence proximity homogeneous assay involving crosslinking (AlphaCL) was performed. When IgG was removed using a Protein G column, the AlphaCL signal was significantly increased, especially in the OIT group, indicating that OIT-induced IgG inhibited the sIgE response. The proportions of cluster of differentiation (CD)4+ cells and CD4+CD25+FoxP3+ cells in mesenteric lymph nodes and spleen were similar between the two groups. These findings indicate that OIT attenuates systemic allergic responses by inhibiting sIgE binding to OVA through increased IgG. Our model is useful for understanding the mechanisms of OIT and optimizing therapeutic strategies for ameliorating food allergies.

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