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Protein Allergenicity in Mice

A Potential Approach for Hazard Identification

Authors


Address for correspondence: Rebecca J. Dearman, Ph.D., Syngenta Central Toxicology Labortory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, England. Voice: 44 01625 514412; fax: 44 01625 582711; rebecca.dearman@syngenta.com.

Abstract

Abstract: Food allergy is an important and common health issue, and there is therefore a need to identify and characterize the sensitizing potential of novel food proteins. Approaches currently used include consideration of structural similarity to, or amino acid sequence homology with, known human allergens; immunologic (generally serologic) cross-reactivity with known allergens; and the measurement of resistance to proteolytic digestion in a simulated gastric fluid. Although these methods provide information that contributes to safety assessment, they do not provide a direct evaluation of the ability of a novel protein to cause allergic sensitization. For this reason considerable interest exists in the design and evaluation of suitable animal models that may provide a more holistic assessment of allergenic potential. The experimental strategy we have adopted is to measure allergenic activity as a function of the ability of proteins to provoke IgG and IgE antibody responses in BALB/c strain mice, a strain that is known to favor immune responses of the quality required for allergic sensitization. To date, emphasis has focused on the characterization of humoral immune responses induced following systemic exposure of mice (by intraperitoneal administration) to the test material. Under these conditions it has been found that proteins known to be associated with food allergy in humans (including peanut proteins and ovalbumin) elicit both specific IgG and IgE antibody responses, measured using enzyme-linked immunosorbant and homologous passive cutaneous anaphylaxis assays, respectively. In contrast, other proteins derived from foods believed to exhibit little or no allergenic potential (such as those derived from the potato), although immunogenic in BALB/c mice (measured as a function of IgG antibody production), either failed to induce IgE antibody responses at all or were associated with only low-grade IgE production at relatively high test concentrations. In comparative analyses, exposure of BALB/c mice to proteins by gavage was found to be less sensitive and discriminatory with respect to the induction of IgE. Experience to date indicates that the inherent sensitizing potential of novel food proteins can be evaluated on the basis of antibody responses stimulated by parenteral exposure of BALB/c strain mice.

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