Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility: potential approaches to safety assessment

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Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility: potential approaches to safety assessment (1)

Food allergies are antigen specific and associated with a limited number of foods; cow’s milk, egg, peanut, soy, wheat, and fish are prominent allergens in children, and adults are most often allergic to peanut, tree nuts, fish, and shellfish. The correlation between allergenicity and digestive stability is not absolute, and because resistance to degradation by acid proteases is used to make regulatory decisions, a more thorough understanding of this relationship is needed. An ideal animal model should mimic human disease with respect to route of exposure, mechanisms underlying the disease, and symptomology. The oral route might be considered the most appropriate route of exposure when developing such a model. This is particularly relevant in light of the clearly established role oral tolerance plays in regulating IgE responses as well as the ambiguous relationship between allergenicity and digestibility. Similarly, IgE is produced upon intradermal exposure to peanut agglutinin without adjuvant. The C3H/HeJ mouse strain has a propensity for high IgE production and has previously been used for mechanistic studies of food-allergic disease.

Oral exposure with CT. Mice were gavaged two or four times at a weekly interval with 1, 2, or 5 mg (total protein) of food extract in plain HBSS or HBSS containing 0.2M sodium bicarbonate, with or without 10 ug CT. Control animals received HBSS and CT only. Blood was collected for antibody analysis 1 week after the last oral exposure. Experimental groups consisted of six to eight animals each.

Spinach was the only extract to demonstrate a clear dose- dependent response upon subcutaneous exposure, with the low (60 ug) and high (300 ug) doses eliciting 1.8- and 2.4-fold increases over naive IgE levels. IgG1 and IgG antibody levels were significantly increased after subcutaneous exposure to all food extracts tested and did not vary by dose.

In contrast, oral exposure to both roasted and raw peanut stimulated significant dose-dependent increases in extract-specific IgE. Egg white elicited more moderate levels of IgE with statistically significant increases observed only at the higher 2 mg dose. ​​Oral exposure to food extracts in the absence of CT did not elicit food-specific antibody responses.

Unlike the ELISA assays, reactivity against roasted peanut in samples from orally exposed animals was notably lower than that from mice exposed subcutaneously.

Consistent with previous results, roasted peanut was the most potent elicitor of IgE. However, under the revised experimental conditions spinach also elicited allergic antibody. IgE levels at the 5 mg dose were statistically significantly elevated compared to na ̈ıve levels, almost to the same extent as those at the 5 mg dose of egg white.

In vitro digestion assays demonstrate that peanut, Brazil nut, and egg white all contain digestion-stable proteins or protein fragments after pepsin treatment, in contrast to turkey, which is completely digested after 15 min.

Oral exposure of mice to allergenic (shrimp, peanut, walnut, cashew, and cod) versus nonallergenic (rice, chicken, and beef) food extracts with CT. High levels of IgE and IgG were generated in response to all allergens tested except cod, which elicited minimal IgE and lower IgG as did the nonallergens.

1. C. C. Bowman, M. K. Selgrade, Differences in allergenic potential of food extracts following oral exposure in mice reflect differences in digestibility: potential approaches to safety assessment. Toxicol. Sci. 102, 100–109 (2008).

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