Guidance on allergenicity assessment of genetically modified plants

Abstract

This document provides supplementary guidance on specific topics for the allergenicity risk assessment of genetically modified plants. In particular, it supplements general recommendations outlined in previous EFSA GMO Panel guidelines and Implementing Regulation (EU) No 503/2013. The topics addressed are non-IgE-mediated adverse immune reactions to foods, in vitro protein digestibility tests and endogenous allergenicity. New scientific and regulatory developments regarding these three topics are described in this document. Considerations on the practical implementation of those developments in the risk assessment of genetically modified plants are discussed and recommended, where appropriate.

Keywords: GMO; allergenicity assessment; endogenous allergenicity; guidance; newly expressed proteins.

Figure 1

Stepwise approach for risk assessment

Figure 2

Search for sequence identity

Figure 3

Q/E‐X1‐P‐X2 motif: possible combinations for the Q/E‐X1‐P‐X2 motif found in the large majority of identified immunogenic gluten‐derived epitopes. It was noted that, while position 1 is always either glutamic acid (E) or glutamine (Q) and position 3 always consists of a proline (P), also positions 2 (X1) and 4 (X2) are restricted to certain amino acids

Figure 4

Endogenous allergenicity workflow for the selection of relevant allergens in soybean

Figure A.1

Shown is a side view of two peptides, one a gliadin T‐cell epitope (top panel) while the other is a peptide derived from a self‐antigen (lower panel). The side chains of the amino acids that point downwards anchor the peptide to the HLA‐DQ‐molecule, the upward‐pointing amino acids can be contacted by the T‐cell receptor. Even though the peptide share some sequence similarity (P at p1, L at P7, P at p8, large amino acid at p2), there are several features that are predicted to prohibit a functional interaction between a gliadin specific T‐cell receptor and the self‐peptide, like an overall different conformation and the presence of a large amino acids at p5 (Q) instead of the much smaller proline (P) in the gliadin peptide (taken from Wiesner et al., 2008)

Figure B.1

Illustrative examples of in vitro gastrointestinal test conditions and proposed gastrointestinal conditions for the interim phase

Figure B.2

Example of possible scenarios resulting from the in vitro digestibility tests and subsequent data interpretation