Assessment of the inherent allergenic potential of proteins in mice.

Abstract

There is considerable interest in the design of approaches that will permit the accurate identification and characterization of proteins that have the inherent potential to induce sensitization and cause food allergy. Among the methods used currently as part of such assessments are consideration of structural similarity to, or amino acid sequence homology with, known human allergens; whether there exists immunologic cross-reactivity with known allergens; and measurement of resistance to proteolytic digestion in a simulated gastric fluid. Although such approaches provide information that will contribute to a safety assessment, they do not--either individually or collectively--provide a direct evaluation of the ability of a novel protein to cause allergic sensitization. For this reason, work is in progress to design and evaluate suitable animal models that will provide a more holistic assessment of allergenic potential. In this laboratory, the approach we have taken has been to examine the characteristics of immune responses induced in mice following parenteral (intraperitoneal) exposure to test proteins. The basis of this method is to determine simultaneously the overall immunogenic potential of proteins [measured as a function of immunoglobulin (Ig) G antibody responses] and to compare this with their ability to provoke IgE antibody production, IgE being the antibody that effects allergic sensitization. Although this approach has not yet been evaluated fully, the results available to date suggest that it will be possible to distinguish proteins that have the inherent potential to induce allergic sensitization from those that do not. In this article we summarize progress to date in the context of the scientific background against which such methods are being developed.

Anti-inflammatory effects of ivermectin in mouse model of allergic asthma

“…In mice, IgG1 is an anaphylactic antibody that is co-regulated with IgE via the IL-4/Th2 pathway, which may explain the use of IgG1 to assess immunogenicity or adjuvant effects in several murine systems [26,27]. Our data also show that ivermectin inhibited OVA-specific IgG1 production.…”

Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl)phthalate and ovalbumin in BALB/c mice

“…Furthermore, IgG1 in mice is an anaphylactic antibody (Oshiba et al, 1996), but only in combinations with high allergen doses (Finkelman et al, 2005). IgG1 is co-regulated with IgE via the IL-4/Th2 path- way (Purkerson and Isakson, 1992), which may explain the use of IgG1 to assess immunogenicity or adjuvant effects in several murine systems (Kimber et al, 2003;Robinson et al, 1996;Yanagisawa et al, 2006) and as a risk factor for developing an IgE response in humans. Overall, the extent to which the IgG1 response should be considered a protective response or a risk factor for development of IgE is not clear at present.…”

A Single Oral Sensitization to Peanut without Adjuvant Leads to Anaphylaxis in Mice

“…Moreover, no use of adjuvant allowed focusing on the true intrinsic peanut allergenicity. Indeed, the use of adjuvant should be taken into consideration with caution in the model of food allergy, because it is possible that it confers on nonallergic proteins the ability to cause sensitization, thus creating false positives [24]. However, little data is available to substantiate this hypothesis.…”