A novel model of sensitization and oral tolerance to peanut protein

Abstract

SUMMARYThe prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens.

Impact of CD40 Ligand, B Cells, and Mast Cells in Peanut-Induced Anaphylactic Responses

“…The recent development of murine models of peanut-induced anaphylaxis (PIA) that mimic physiologic and immunologic features of human PA has facilitated both understanding of the underlying mechanisms and evaluation of potential therapeutic approaches (11)(12)(13). An important focus of these models has been on the role of Th2 responses in the regulation of sensitization (14 -16) and, subsequently, therapeutic strategies to redirect immune responses away from Th2 (17,18).…”

Early Introduction of Foods for Food Allergy Prevention

“…In a murine model of food allergy, low-dose oral exposure to OVA and peanuts resulted in enhanced immune responses following immunisation with OVA or peanuts, while feeding high doses prior to immunisation led to the development of persistent antigen-specific oral tolerance [14]. The relevance of these findings to the development of oral tolerance or food allergy in humans is not yet known.…”

Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins

“…the exact opposite of the basis of animal tests). This same principle is the message of a sensitization and oral tolerance study to peanut performed in mice, which is more tailored toward the higher molecular weight allergens in food allergy (Strid et al, 2004).…”