Allergic sensitization: screening methods

Abstract

Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute.

Figure 1

Overlap of the X-ray crystal structures of natural Der p 1 in complex with an Fab of the mAb 4C1 (cyan) with the X-ray crystal structure of Der f 1 in complex with the same antibody fragment (violet). The structures show the molecular basis of cross-reactivity between both dust mite allergens: the Fab recognizes the same area in Der p 1 and Der f 1, which is a conformational epitope overlapping with an IgE antibody binding site [24].

Figure 2

Testing strategy for determining the lung sensitizing capacity and relative potency of proteins.

Figure 3

Testing strategy for determining the lung sensitizing capacity and relative potency of proteins.

Figure 4

Model example: specific IgG1 and IgE measured by direct and capture ELISA, respectively, after oral doing of Brown Norway rats for 35 days without adjuvant with two related proteins.